LIVIVO - Search results -

Search results

Result 1 - 10 of total 17

Search options

Article ; Online: Selective Pharmaceutical Inhibition of PARP14 Mitigates Allergen-Induced IgE and Mucus Overproduction in a Mouse Model of Pulmonary Allergic Response.

Eddie, Alex M / Chen, Kevin W / Schenkel, Laurie B / Swinger, Kerren K / Molina, Jennifer R / Kunii, Kaiko / Raybuck, Ariel L / Keilhack, Heike / Gibson-Corley, Katherine N / Niepel, Mario / Peebles, R Stokes / Boothby, Mark R / Cho, Sung Hoon

ImmunoHorizons

2022 Volume 6, Issue 7, Page(s) 432–446

Abstract: The type 2 cytokines IL-4 and IL-13, which share use of an IL-4 receptor α-chain and its nuclear induction of the transcription factor STAT6, are crucial in elicitation and maintenance of allergic conditions including asthma. STAT6 binds poly(ADP-ribose) ...

Abstract	The type 2 cytokines IL-4 and IL-13, which share use of an IL-4 receptor α-chain and its nuclear induction of the transcription factor STAT6, are crucial in elicitation and maintenance of allergic conditions including asthma. STAT6 binds poly(ADP-ribose) polymerase (PARP)14, an ADP-ribosyl monotransferase. Elimination of PARP14 by gene targeting led to attenuation of OVA-specific allergic lung inflammation. However, PARP14 has multiple functional domains apart from the portion that catalyzes ADP-ribosylation, and it is not clear whether inhibition of the catalytic function has any biological consequence. Using BALB/c mice sensitized to the allergen
MeSH term(s)	Allergens ; Animals ; Asthma/drug therapy ; Disease Models, Animal ; Immunoglobulin E ; Mice ; Mucus/metabolism ; Pharmaceutical Preparations/metabolism ; Poly(ADP-ribose) Polymerase Inhibitors/metabolism ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Poly(ADP-ribose) Polymerases/genetics ; Poly(ADP-ribose) Polymerases/metabolism ; Poly(ADP-ribose) Polymerases/therapeutic use
Chemical Substances	Allergens ; Pharmaceutical Preparations ; Poly(ADP-ribose) Polymerase Inhibitors ; Immunoglobulin E (37341-29-0) ; Parp14 protein, mouse (EC 2.4.2.30) ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30)
Language	English
Publishing date	2022-07-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2573-7732
ISSN (online)	2573-7732
DOI	10.4049/immunohorizons.2100107
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: A potent and selective PARP14 inhibitor decreases protumor macrophage gene expression and elicits inflammatory responses in tumor explants.

Cell chemical biology

2021 Volume 28, Issue 8, Page(s) 1158–1168.e13

Abstract: PARP14 has been implicated by genetic knockout studies to promote protumor macrophage polarization and suppress the antitumor inflammatory response due to its role in modulating interleukin-4 (IL-4) and interferon-γ signaling pathways. Here, we describe ... ...

Abstract	PARP14 has been implicated by genetic knockout studies to promote protumor macrophage polarization and suppress the antitumor inflammatory response due to its role in modulating interleukin-4 (IL-4) and interferon-γ signaling pathways. Here, we describe structure-based design efforts leading to the discovery of a potent and highly selective PARP14 chemical probe. RBN012759 inhibits PARP14 with a biochemical half-maximal inhibitory concentration of 0.003 μM, exhibits >300-fold selectivity over all PARP family members, and its profile enables further study of PARP14 biology and disease association both in vitro and in vivo. Inhibition of PARP14 with RBN012759 reverses IL-4-driven protumor gene expression in macrophages and induces an inflammatory mRNA signature similar to that induced by immune checkpoint inhibitor therapy in primary human tumor explants. These data support an immune suppressive role of PARP14 in tumors and suggest potential utility of PARP14 inhibitors in the treatment of cancer.
MeSH term(s)	Animals ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Dose-Response Relationship, Drug ; Female ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/genetics ; HEK293 Cells ; Humans ; Inflammation/drug therapy ; Inflammation/genetics ; Inflammation/metabolism ; Interleukin-4/antagonists & inhibitors ; Interleukin-4/genetics ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/genetics ; Kidney Neoplasms/metabolism ; Macrophages/drug effects ; Macrophages/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Models, Molecular ; Molecular Structure ; Poly(ADP-ribose) Polymerases/genetics ; Poly(ADP-ribose) Polymerases/metabolism ; RAW 264.7 Cells ; RNA, Messenger/drug effects ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
Chemical Substances	Antineoplastic Agents ; RNA, Messenger ; Interleukin-4 (207137-56-2) ; PARP14 protein, human (EC 2.4.2.30) ; Parp14 protein, mouse (EC 2.4.2.30) ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30)
Language	English
Publishing date	2021-03-10
Publishing country	United States
Document type	Journal Article
ISSN	2451-9448
ISSN (online)	2451-9448
DOI	10.1016/j.chembiol.2021.02.010
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity.

Gozgit, Joseph M / Vasbinder, Melissa M / Abo, Ryan P / Kunii, Kaiko / Kuplast-Barr, Kristy G / Gui, Bin / Lu, Alvin Z / Molina, Jennifer R / Minissale, Elena / Swinger, Kerren K / Wigle, Tim J / Blackwell, Danielle J / Majer, Christina R / Ren, Yue / Niepel, Mario / Varsamis, Zacharenia A / Nayak, Sunaina P / Bamberg, Ellen / Mo, Jan-Rung /

Church, W David / Mady, Ahmed S A / Song, Jeff / Utley, Luke / Rao, Patricia E / Mitchison, Timothy J / Kuntz, Kevin W / Richon, Victoria M / Keilhack, Heike

Cancer cell

2021 Volume 39, Issue 9, Page(s) 1214–1226.e10

Abstract: PARP7 is a monoPARP that catalyzes the transfer of single units of ADP-ribose onto substrates to change their function. Here, we identify PARP7 as a negative regulator of nucleic acid sensing in tumor cells. Inhibition of PARP7 restores type I interferon ...

Abstract	PARP7 is a monoPARP that catalyzes the transfer of single units of ADP-ribose onto substrates to change their function. Here, we identify PARP7 as a negative regulator of nucleic acid sensing in tumor cells. Inhibition of PARP7 restores type I interferon (IFN) signaling responses to nucleic acids in tumor models. Restored signaling can directly inhibit cell proliferation and activate the immune system, both of which contribute to tumor regression. Oral dosing of the PARP7 small-molecule inhibitor, RBN-2397, results in complete tumor regression in a lung cancer xenograft and induces tumor-specific adaptive immune memory in an immunocompetent mouse cancer model, dependent on inducing type I IFN signaling in tumor cells. PARP7 is a therapeutic target whose inhibition induces both cancer cell-autonomous and immune stimulatory effects via enhanced IFN signaling. These data support the targeting of a monoPARP in cancer and introduce a potent and selective PARP7 inhibitor to enter clinical development.
MeSH term(s)	Adaptive Immunity/drug effects ; Animals ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drug Resistance, Neoplasm/drug effects ; HEK293 Cells ; HeLa Cells ; Humans ; Interferon Type I/metabolism ; Mice ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Nucleoside Transport Proteins/genetics ; Nucleoside Transport Proteins/metabolism ; Signal Transduction/drug effects ; Small Molecule Libraries/administration & dosage ; Small Molecule Libraries/pharmacology ; Tumor Escape/drug effects ; Xenograft Model Antitumor Assays
Chemical Substances	Interferon Type I ; Nucleoside Transport Proteins ; Small Molecule Libraries ; TiPARP protein, human
Language	English
Publishing date	2021-07-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2021.06.018
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5650: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 104: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: MTAP Deletions in Cancer Create Vulnerability to Targeting of the MAT2A/PRMT5/RIOK1 Axis.

Marjon, Katya / Cameron, Michael J / Quang, Phong / Clasquin, Michelle F / Mandley, Everton / Kunii, Kaiko / McVay, Michael / Choe, Sung / Kernytsky, Andrew / Gross, Stefan / Konteatis, Zenon / Murtie, Joshua / Blake, Michelle L / Travins, Jeremy / Dorsch, Marion / Biller, Scott A / Marks, Kevin M

Cell reports

2016 Volume 15, Issue 3, Page(s) 574–587

Abstract: Homozygous deletions of p16/CDKN2A are prevalent in cancer, and these mutations commonly involve co-deletion of adjacent genes, including methylthioadenosine phosphorylase (MTAP). Here, we used shRNA screening and identified the metabolic enzyme, ... ...

Abstract	Homozygous deletions of p16/CDKN2A are prevalent in cancer, and these mutations commonly involve co-deletion of adjacent genes, including methylthioadenosine phosphorylase (MTAP). Here, we used shRNA screening and identified the metabolic enzyme, methionine adenosyltransferase II alpha (MAT2A), and the arginine methyltransferase, PRMT5, as vulnerable enzymes in cells with MTAP deletion. Metabolomic and biochemical studies revealed a mechanistic basis for this synthetic lethality. The MTAP substrate methylthioadenosine (MTA) accumulates upon MTAP loss. Biochemical profiling of a methyltransferase enzyme panel revealed that MTA is a potent and selective inhibitor of PRMT5. MTAP-deleted cells have reduced PRMT5 methylation activity and increased sensitivity to PRMT5 depletion. MAT2A produces the PRMT5 substrate S-adenosylmethionine (SAM), and MAT2A depletion reduces growth and PRMT5 methylation activity selectively in MTAP-deleted cells. Furthermore, this vulnerability extends to PRMT5 co-complex proteins such as RIOK1. Thus, the unique biochemical features of PRMT5 create an axis of targets vulnerable in CDKN2A/MTAP-deleted cancers.
MeSH term(s)	Adenosine/analogs & derivatives ; Adenosine/metabolism ; Antigens, Neoplasm/metabolism ; Gene Deletion ; Genomics ; HCT116 Cells ; Humans ; Methionine Adenosyltransferase/metabolism ; Multiprotein Complexes/metabolism ; Neoplasms/enzymology ; Neoplasms/metabolism ; Protein-Arginine N-Methyltransferases/metabolism ; Protein-Serine-Threonine Kinases/metabolism ; Purine-Nucleoside Phosphorylase/deficiency ; Purine-Nucleoside Phosphorylase/metabolism ; RNA, Small Interfering/metabolism ; Signal Transduction ; Thionucleosides/metabolism
Chemical Substances	Antigens, Neoplasm ; Multiprotein Complexes ; RNA, Small Interfering ; Thionucleosides ; 2-methylthioadenosine (4105-39-9) ; PRMT5 protein, human (EC 2.1.1.319) ; Protein-Arginine N-Methyltransferases (EC 2.1.1.319) ; Purine-Nucleoside Phosphorylase (EC 2.4.2.1) ; 5'-methylthioadenosine phosphorylase (EC 2.4.2.28) ; MAT2A protein, human (EC 2.5.1.6) ; Methionine Adenosyltransferase (EC 2.5.1.6) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; RIOK1 protein, human (EC 2.7.11.1) ; Adenosine (K72T3FS567)
Language	English
Publishing date	2016-04-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2016.03.043
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: A role for iNOS in fasting hyperglycemia and impaired insulin signaling in the liver of obese diabetic mice.

Fujimoto, Masaki / Shimizu, Nobuyuki / Kunii, Kaiko / Martyn, J A Jeevendra / Ueki, Kohjiro / Kaneki, Masao

Diabetes

2005 Volume 54, Issue 5, Page(s) 1340–1348

Abstract: Chronic inflammation has been postulated to play an important role in the pathogenesis of insulin resistance. Inducible nitric oxide synthase (iNOS) has been implicated in many human diseases associated with inflammation. iNOS deficiency was shown to ... ...

Abstract	Chronic inflammation has been postulated to play an important role in the pathogenesis of insulin resistance. Inducible nitric oxide synthase (iNOS) has been implicated in many human diseases associated with inflammation. iNOS deficiency was shown to prevent high-fat diet-induced insulin resistance in skeletal muscle but not in the liver. A role for iNOS in fasting hyperglycemia and hepatic insulin resistance, however, remains to be investigated in obesity-related diabetes. To address this issue, we examined the effects of a specific inhibitor for iNOS, L-NIL, in obese diabetic (ob/ob) mice. iNOS expression was increased in the liver of ob/ob mice compared with wild-type mice. Treatment with iNOS inhibitor reversed fasting hyperglycemia with concomitant amelioration of hyperinsulinemia and improved insulin sensitivity in ob/ob mice. iNOS inhibitor also increased the protein expression of insulin receptor substrate (IRS)-1 and -2 1.5- and 2-fold, respectively, and enhanced IRS-1- and IRS-2-mediated insulin signaling in the liver of ob/ob mice. Exposure to NO donor and ectopically expressed iNOS decreased the protein expression of IRS-1 and -2 in cultured hepatocytes. These results suggest that iNOS plays a role in fasting hyperglycemia and contributes to hepatic insulin resistance in ob/ob mice.
MeSH term(s)	Animals ; Cells, Cultured ; Diabetes Mellitus, Type 2/enzymology ; Enzyme Inhibitors/pharmacology ; Fasting ; Hepatocytes/enzymology ; Hepatocytes/physiology ; Hyperglycemia/enzymology ; Hyperglycemia/physiopathology ; Insulin/physiology ; Insulin Resistance ; Liver/enzymology ; Liver/physiology ; Lysine/analogs & derivatives ; Lysine/pharmacology ; Male ; Mice ; Mice, Obese ; Nitric Oxide Donors/pharmacology ; Nitric Oxide Synthase/antagonists & inhibitors ; Nitric Oxide Synthase/metabolism ; Nitric Oxide Synthase Type II ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction/physiology
Chemical Substances	Enzyme Inhibitors ; Insulin ; N(6)-(1-iminoethyl)lysine ; Nitric Oxide Donors ; Nitric Oxide Synthase (EC 1.14.13.39) ; Nitric Oxide Synthase Type II (EC 1.14.13.39) ; Nos2 protein, mouse (EC 1.14.13.39) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2005-04-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/diabetes.54.5.1340
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.175: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: FGFR2-amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival.

Kunii, Kaiko / Davis, Lenora / Gorenstein, Julie / Hatch, Harold / Yashiro, Masakazu / Di Bacco, Alessandra / Elbi, Cem / Lutterbach, Bart

Cancer research

2008 Volume 68, Issue 7, Page(s) 2340–2348

Abstract: We have identified a critical role for amplified FGFR2 in gastric cancer cell proliferation and survival. In a panel of gastric cancer cell lines, fibroblast growth factor receptor 2 (FGFR2) was overexpressed and tyrosine phosphorylated selectively in ... ...

Abstract	We have identified a critical role for amplified FGFR2 in gastric cancer cell proliferation and survival. In a panel of gastric cancer cell lines, fibroblast growth factor receptor 2 (FGFR2) was overexpressed and tyrosine phosphorylated selectively in FGFR2-amplified cell lines KatoIII, Snu16, and OCUM-2M. FGFR2 kinase inhibition by a specific small-molecule inhibitor resulted in selective and potent growth inhibition in FGFR2-amplified cell lines, resulting in growth arrest in KatoIII cells and prominent induction of apoptosis in both Snu16 and OCUM-2M cells. FGFR2-amplified cell lines also contained elevated phosphotyrosine in EGFR, Her2, and Erbb3, but the elevated phosphorylation in EGFR could not be inhibited by gefitinib or erlotinib. We show that the elevated EGFR, Her2, and Erbb3 phosphotyrosine is dependent on FGFR2, revealing EGFR family kinases to be downstream targets of amplified FGFR2. Moreover, shRNA to Erbb3 resulted in a loss of proliferation, confirming a functional role for the activated EGFR signaling pathway. These results reveal that both the FGFR2 and EGFR family signaling pathways are activated in FGFR2-amplified gastric cancer cell lines to drive cell proliferation and survival. Inhibitors of FGFR2 or Erbb3 signaling may have therapeutic efficacy in the subset of gastric cancers containing FGFR2 amplification.
MeSH term(s)	Apoptosis/drug effects ; Apoptosis/genetics ; Cell Growth Processes/genetics ; Cell Line, Tumor ; Gene Amplification ; Humans ; Phosphorylation ; Pyrimidines/pharmacology ; RNA, Small Interfering/genetics ; Receptor, ErbB-3/metabolism ; Receptor, Fibroblast Growth Factor, Type 2/antagonists & inhibitors ; Receptor, Fibroblast Growth Factor, Type 2/biosynthesis ; Receptor, Fibroblast Growth Factor, Type 2/genetics ; Receptor, Fibroblast Growth Factor, Type 2/metabolism ; Signal Transduction ; Stomach Neoplasms/enzymology ; Stomach Neoplasms/genetics ; Stomach Neoplasms/pathology
Chemical Substances	PD 173074 ; Pyrimidines ; RNA, Small Interfering ; Receptor, ErbB-3 (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 2 (EC 2.7.10.1)
Language	English
Publishing date	2008-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-07-5229
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.135/5: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Involvement of the serotonergic system in orexin-induced behavioral alterations in rats.

Matsuzaki, Ichiyo / Sakurai, Takeshi / Kunii, Kaiko / Nakamura, Toshiaki / Yanagisawa, Masashi / Goto, Katsutoshi

Regulatory peptides

2002 Volume 104, Issue 1-3, Page(s) 119–123

Abstract: We have demonstrated involvement of the serotonergic system in orexin-induced behavioral responses in rats. Orexin-A and -B (hypocretin-1 and -2) significantly increased total locomotor activity when administered centrally. They also induced behavioral ... ...

Abstract	We have demonstrated involvement of the serotonergic system in orexin-induced behavioral responses in rats. Orexin-A and -B (hypocretin-1 and -2) significantly increased total locomotor activity when administered centrally. They also induced behavioral alterations; increasing grooming, face washing and wet dog shaking in rats. Haloperidol inhibited orexin-induced hyperlocomotion and these behavioral alterations. Serotonin antagonists, ritanserin and metergoline, did not attenuate orexin-induced hyperlocomotion but partly inhibited orexin-induced behavioral alterations. These results suggest that the dopaminergic system might be involved in orexin-induced hyperlocomotion, while both the serotonergic system as well as the dopaminergic system might be involved in orexin-induced behavioral responses.
MeSH term(s)	Animals ; Carrier Proteins/pharmacology ; Dopamine/physiology ; Dopamine Antagonists/pharmacology ; Grooming/drug effects ; Grooming/physiology ; Haloperidol/pharmacology ; Injections, Intraventricular/methods ; Intracellular Signaling Peptides and Proteins ; Locomotion/drug effects ; Locomotion/physiology ; Male ; Metergoline/pharmacology ; Neuropeptides/pharmacology ; Orexins ; Rats ; Rats, Wistar ; Ritanserin/pharmacology ; Serotonin/physiology ; Serotonin Antagonists/pharmacology
Chemical Substances	Carrier Proteins ; Dopamine Antagonists ; Intracellular Signaling Peptides and Proteins ; Neuropeptides ; Orexins ; Serotonin Antagonists ; Ritanserin (145TFV465S) ; Metergoline (1501393LY5) ; Serotonin (333DO1RDJY) ; Haloperidol (J6292F8L3D) ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2002-02-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	225685-x
ISSN	1873-1686 ; 0167-0115
ISSN (online)	1873-1686
ISSN	0167-0115
DOI	10.1016/s0167-0115(01)00355-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1593: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Evidence of mTOR Activation by an AKT-Independent Mechanism Provides Support for the Combined Treatment of PTEN-Deficient Prostate Tumors with mTOR and AKT Inhibitors.

Zhang, Weisheng / Haines, Brian B / Efferson, Clay / Zhu, Joe / Ware, Chris / Kunii, Kaiko / Tammam, Jennifer / Angagaw, Minilik / Hinton, Marlene C / Keilhack, Heike / Paweletz, Cloud P / Zhang, Theresa / Winter, Chris / Sathyanarayanan, Sriram / Cheng, Jonathan / Zawel, Leigh / Fawell, Stephen / Gilliland, Gary / Majumder, Pradip K

Translational oncology

2012 Volume 5, Issue 6, Page(s) 422–429

Abstract: Activation of the phosphoinositide 3-kinase pathway is commonly observed in human prostate cancer. Loss of function of phosphatase and tensin homolog (PTEN) is associated with the activation of AKT and mammalian target of rapamycin (mTOR) in many cancer ... ...

Abstract	Activation of the phosphoinositide 3-kinase pathway is commonly observed in human prostate cancer. Loss of function of phosphatase and tensin homolog (PTEN) is associated with the activation of AKT and mammalian target of rapamycin (mTOR) in many cancer cell lines as well as in other model systems. However, activation of mTOR is also dependent of kinases other than AKT. Here, we show that activation of mTOR is not dependent on AKT in a prostate-specific PTEN-deficient mouse model of prostate cancer. Pathway bifurcation of AKT and mTOR was noted in both mouse and human prostate tumors. We demonstrated for the first time that cotargeting mTOR and AKT with ridaforolimus/MK-8669 and M1K-2206, respectively, delivers additive antitumor effects in vivo when compared to single agents. Our preclinical data suggest that the combination of AKT and mTOR inhibitors might be more effective in treating prostate cancer patients than current treatment regimens or either treatment alone.
Language	English
Publishing date	2012-12-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2443840-6
ISSN	1936-5233
ISSN	1936-5233
DOI	10.1593/tlo.12241
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Type II phosphatidylinositol 4-kinase beta is a cytosolic and peripheral membrane protein that is recruited to the plasma membrane and activated by Rac-GTP.

Wei, Yong Jie / Sun, Hui Qiao / Yamamoto, Masaya / Wlodarski, Pawel / Kunii, Kaiko / Martinez, Manuel / Barylko, Barbara / Albanesi, Joseph P / Yin, Helen L

The Journal of biological chemistry

2002 Volume 277, Issue 48, Page(s) 46586–46593

Abstract: Phosphoinositides have a pivotal role as precursors to important second messengers and as bona fide signaling and scaffold targeting molecules. Phosphatidylinositol 4-kinases (PtdIns 4-kinases or PI4Ks) are at the apex of the phosphoinsitide cascade. ... ...

Abstract	Phosphoinositides have a pivotal role as precursors to important second messengers and as bona fide signaling and scaffold targeting molecules. Phosphatidylinositol 4-kinases (PtdIns 4-kinases or PI4Ks) are at the apex of the phosphoinsitide cascade. Sequence analysis revealed that mammalian cells contain two type II PtdIns 4-kinase isoforms, now termed PI4KIIalpha and PI4KIIbeta. PI4KIIalpha was cloned first. It is tightly membrane-associated and behaves as an integral membrane protein. In this study, we cloned PI4KIIbeta and compared the two isoforms by monitoring the distribution of endogenous and overexpressed proteins, their modes of association with membranes, their response to growth factor stimulation or Rac-GTP activation, and their kinetic properties. We find that the two kinases have different properties. PI4KIIbeta is primarily cytosolic, and it associates peripherally with plasma membranes, endoplasmic reticulum, and the Golgi. In contrast, PI4KIIalpha is primarily Golgi-associated. Platelet-derived growth factor promotes PI4KIIbeta recruitment to membrane ruffles. This effect is potentially mediated through Rac; overexpression of the constitutively active RacV12 induces membrane ruffling, increases PI4KIIbeta translocation to the plasma membrane, and stimulates its activity. The dominant-negative RacN17 blocks plasma membrane association and inhibits activity. RacV12 does not boost the catalytic activity of PI4KIIalpha further, probably because it is constitutively membrane-bound and already activated. Membrane recruitment is an important mechanism for PI4KIIbeta activation, because microsome-bound PI4KIIbeta is 16 times more active than cytosolic PI4KIIbeta. Membrane-associated PI4KIIbeta is as active as membrane-associated PI4KIIalpha and has essentially identical kinetic properties. We conclude that PI4KIIalpha and PI4KIIbeta may have partially overlapping, but not identical, functions. PI4KIIbeta is activated strongly by membrane association to stimulate phosphatidylinositol 4,5-bisphosphate synthesis at the plasma membrane. These findings provide new insight into how phosphoinositide cascades are propagated in cells.
MeSH term(s)	1-Phosphatidylinositol 4-Kinase/genetics ; 1-Phosphatidylinositol 4-Kinase/metabolism ; Cell Membrane/metabolism ; Cloning, Molecular ; Cytosol/enzymology ; DNA, Complementary ; Enzyme Activation ; Guanosine Triphosphate/pharmacology ; Humans ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Subcellular Fractions/enzymology
Chemical Substances	DNA, Complementary ; Membrane Proteins ; Guanosine Triphosphate (86-01-1) ; 1-Phosphatidylinositol 4-Kinase (EC 2.7.1.67)
Language	English
Publishing date	2002-09-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M206860200
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Cancer-Associated SF3B1 Hotspot Mutations Induce Cryptic 3' Splice Site Selection through Use of a Different Branch Point.

Darman, Rachel B / Seiler, Michael / Agrawal, Anant A / Lim, Kian H / Peng, Shouyong / Aird, Daniel / Bailey, Suzanna L / Bhavsar, Erica B / Chan, Betty / Colla, Simona / Corson, Laura / Feala, Jacob / Fekkes, Peter / Ichikawa, Kana / Keaney, Gregg F / Lee, Linda / Kumar, Pavan / Kunii, Kaiko / MacKenzie, Crystal /

Matijevic, Mark / Mizui, Yoshiharu / Myint, Khin / Park, Eun Sun / Puyang, Xiaoling / Selvaraj, Anand / Thomas, Michael P / Tsai, Jennifer / Wang, John Y / Warmuth, Markus / Yang, Hui / Zhu, Ping / Garcia-Manero, Guillermo / Furman, Richard R / Yu, Lihua / Smith, Peter G / Buonamici, Silvia

Cell reports

2015 Volume 13, Issue 5, Page(s) 1033–1045

Abstract: Recurrent mutations in the spliceosome are observed in several human cancers, but their functional and therapeutic significance remains elusive. SF3B1, the most frequently mutated component of the spliceosome in cancer, is involved in the recognition of ... ...

Abstract	Recurrent mutations in the spliceosome are observed in several human cancers, but their functional and therapeutic significance remains elusive. SF3B1, the most frequently mutated component of the spliceosome in cancer, is involved in the recognition of the branch point sequence (BPS) during selection of the 3' splice site (ss) in RNA splicing. Here, we report that common and tumor-specific splicing aberrations are induced by SF3B1 mutations and establish aberrant 3' ss selection as the most frequent splicing defect. Strikingly, mutant SF3B1 utilizes a BPS that differs from that used by wild-type SF3B1 and requires the canonical 3' ss to enable aberrant splicing during the second step. Approximately 50% of the aberrantly spliced mRNAs are subjected to nonsense-mediated decay resulting in downregulation of gene and protein expression. These findings ascribe functional significance to the consequences of SF3B1 mutations in cancer.
MeSH term(s)	Alleles ; Alternative Splicing ; Amino Acid Sequence ; Base Sequence ; HEK293 Cells ; Humans ; Molecular Sequence Data ; Mutation ; Mutation Rate ; Neoplasms/genetics ; Nonsense Mediated mRNA Decay ; Phosphoproteins/chemistry ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; RNA Splicing Factors ; Ribonucleoprotein, U2 Small Nuclear/chemistry ; Ribonucleoprotein, U2 Small Nuclear/genetics ; Ribonucleoprotein, U2 Small Nuclear/metabolism
Chemical Substances	Phosphoproteins ; RNA Splicing Factors ; Ribonucleoprotein, U2 Small Nuclear ; SF3B1 protein, human
Language	English
Publishing date	2015-11-3
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2015.09.053
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito