LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 6 of total 6

Search options

  1. Article: p53 Acetylation: Regulation and Consequences.

    Reed, Sara M / Quelle, Dawn E

    Cancers

    2014  Volume 7, Issue 1, Page(s) 30–69

    Abstract: Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional ... ...

    Abstract Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo evidence from mouse models questions the importance of p53 acetylation (at least at certain sites) as well as canonical p53 functions (cell cycle arrest, senescence and apoptosis) to tumor suppression. This review discusses the cumulative findings regarding p53 acetylation, with a focus on the acetyltransferases that modify p53 and the mechanisms regulating their activity. We also evaluate what is known regarding the influence of other post-translational modifications of p53 on its acetylation, and conclude with the current outlook on how p53 acetylation affects tumor suppression. Due to redundancies in p53 control and growing understanding that individual modifications largely fine-tune p53 activity rather than switch it on or off, many questions still remain about the physiological importance of p53 acetylation to its role in preventing cancer.
    Language English
    Publishing date 2014-12-23
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers7010030
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    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.

  2. Article ; Online: ARF sees Pdgfrβ through the miR.

    Reed, Sara M / Quelle, Frederick W / Quelle, Dawn E

    Cell cycle (Georgetown, Tex.)

    2014  Volume 13, Issue 10, Page(s) 1520–1521

    MeSH term(s) Animals ; Cell Cycle Checkpoints/genetics ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; MicroRNAs/metabolism
    Chemical Substances Cyclin-Dependent Kinase Inhibitor p16 ; MicroRNAs
    Language English
    Publishing date 2014-04-22
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    DOI 10.4161/cc.28900
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5881: 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)

    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.

  3. Article ; Online: Nuclear interactor of ARF and Mdm2 regulates multiple pathways to activate p53.

    Reed, Sara M / Hagen, Jussara / Tompkins, Van S / Thies, Katie / Quelle, Frederick W / Quelle, Dawn E

    Cell cycle (Georgetown, Tex.)

    2014  Volume 13, Issue 8, Page(s) 1288–1298

    Abstract: The p53 tumor suppressor is controlled by an interactive network of factors that stimulate or inhibit its transcriptional activity. Within that network, Mdm2 functions as the major antagonist of p53 by promoting its ubiquitylation and degradation. ... ...

    Abstract The p53 tumor suppressor is controlled by an interactive network of factors that stimulate or inhibit its transcriptional activity. Within that network, Mdm2 functions as the major antagonist of p53 by promoting its ubiquitylation and degradation. Conversely, Tip60 activates p53 through direct association on target promoters as well as acetylation of p53 at lysine 120 (K120). This study examines the functional relationship between Mdm2 and Tip60 with a novel p53 regulator, NIAM (nuclear interactor of ARF and Mdm2). Previous work showed NIAM can suppress proliferation and activate p53 independently of ARF, indicating that other factors mediate those activities. Here, we demonstrate that NIAM is a chromatin-associated protein that binds Tip60. NIAM can promote p53 K120 acetylation, although that modification is not required for NIAM to inhibit proliferation or induce p53 transactivation of the p21 promoter. Notably, Tip60 silencing showed it contributes to but is not sufficient for NIAM-mediated p53 activation, suggesting other mechanisms are involved. Indeed, growth-inhibitory forms of NIAM also bind to Mdm2, and increased NIAM expression levels disrupt p53-Mdm2 association, inhibit p53 polyubiquitylation, and prevent Mdm2-mediated inhibition of p53 transcriptional activity. Importantly, loss of NIAM significantly impairs p53 activation. Together, these results show that NIAM activates p53 through multiple mechanisms involving Tip60 association and Mdm2 inhibition. Thus, NIAM regulates 2 critical pathways that control p53 function and are altered in human cancers, implying an important role for NIAM in tumorigenesis.
    MeSH term(s) Acetylation ; Animals ; Cell Line ; Cell Line, Tumor ; Cell Proliferation/physiology ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Histone Acetyltransferases/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Lysine Acetyltransferase 5 ; Mice ; Nuclear Proteins/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Proto-Oncogene Proteins c-mdm2/metabolism ; Signal Transduction ; Transcriptional Activation ; Tumor Suppressor Protein p53/metabolism ; Ubiquitination
    Chemical Substances CDKN1A protein, human ; Cyclin-Dependent Kinase Inhibitor p21 ; Intracellular Signaling Peptides and Proteins ; Nuclear Proteins ; TBRG1 protein, human ; Tumor Suppressor Protein p53 ; Histone Acetyltransferases (EC 2.3.1.48) ; KAT5 protein, human (EC 2.3.1.48) ; Lysine Acetyltransferase 5 (EC 2.3.1.48) ; MDM2 protein, human (EC 2.3.2.27) ; Proto-Oncogene Proteins c-mdm2 (EC 2.3.2.27)
    Language English
    Publishing date 2014-02-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    DOI 10.4161/cc.28202
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5881: 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)

    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.

  4. Article ; Online: NIAM-deficient mice are predisposed to the development of proliferative lesions including B-cell lymphomas.

    Reed, Sara M / Hagen, Jussara / Muniz, Viviane P / Rosean, Timothy R / Borcherding, Nick / Sciegienka, Sebastian / Goeken, J Adam / Naumann, Paul W / Zhang, Weizhou / Tompkins, Van S / Janz, Siegfried / Meyerholz, David K / Quelle, Dawn E

    PloS one

    2014  Volume 9, Issue 11, Page(s) e112126

    Abstract: Nuclear Interactor of ARF and Mdm2 (NIAM, gene designation Tbrg1) is a largely unstudied inhibitor of cell proliferation that helps maintain chromosomal stability. It is a novel activator of the ARF-Mdm2-Tip60-p53 tumor suppressor pathway as well as ... ...

    Abstract Nuclear Interactor of ARF and Mdm2 (NIAM, gene designation Tbrg1) is a largely unstudied inhibitor of cell proliferation that helps maintain chromosomal stability. It is a novel activator of the ARF-Mdm2-Tip60-p53 tumor suppressor pathway as well as other undefined pathways important for genome maintenance. To examine its predicted role as a tumor suppressor, we generated NIAM mutant (NIAM(m/m)) mice homozygous for a β-galactosidase expressing gene-trap cassette in the endogenous gene. The mutant mice expressed significantly lower levels of NIAM protein in tissues compared to wild-type animals. Fifty percent of aged NIAM deficient mice (14 to 21 months) developed proliferative lesions, including a uterine hemangioma, pulmonary papillary adenoma, and a Harderian gland adenoma. No age-matched wild-type or NIAM(+/m) heterozygous animals developed lesions. In the spleen, NIAM(m/m) mice had prominent white pulp expansion which correlated with enhanced increased reactive lymphoid hyperplasia and evidence of systemic inflammation. Notably, 17% of NIAM mutant mice had splenic white pulp features indicating early B-cell lymphoma. This correlated with selective expansion of marginal zone B cells in the spleens of younger, tumor-free NIAM-deficient mice. Unexpectedly, basal p53 expression and activity was largely unaffected by NIAM loss in isolated splenic B cells. In sum, NIAM down-regulation in vivo results in a significant predisposition to developing benign tumors or early stage cancers. These mice represent an outstanding platform for dissecting NIAM's role in tumorigenesis and various anti-cancer pathways, including p53 signaling.
    MeSH term(s) Adenoma/genetics ; Animals ; Cell Proliferation/genetics ; Cell Transformation, Neoplastic/genetics ; DNA-Binding Proteins/genetics ; Down-Regulation ; Female ; Genetic Predisposition to Disease ; Hemangioma/genetics ; Humans ; Hyperplasia/genetics ; Lymphoma, B-Cell/genetics ; Male ; Mice ; Mice, Transgenic ; Signal Transduction ; Tumor Suppressor Protein p53
    Chemical Substances DNA-Binding Proteins ; Niam protein, mouse ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2014-11-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0112126
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    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.

  5. Article: RABL6A Promotes Oxaliplatin Resistance in Tumor Cells and Is a New Marker of Survival for Resected Pancreatic Ductal Adenocarcinoma Patients.

    Muniz, Viviane P / Askeland, Ryan W / Zhang, Xuefeng / Reed, Sara M / Tompkins, Van S / Hagen, Jussara / McDowell, Bradley D / Button, Anna / Smith, Brian J / Weydert, Jamie A / Mezhir, James J / Quelle, Dawn E

    Genes & cancer

    2013  Volume 4, Issue 7-8, Page(s) 273–284

    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is characterized by early recurrence following pancreatectomy, rapid progression, and chemoresistance. Novel prognostic and predictive biomarkers are urgently needed to both stratify patients for clinical trials ... ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by early recurrence following pancreatectomy, rapid progression, and chemoresistance. Novel prognostic and predictive biomarkers are urgently needed to both stratify patients for clinical trials and select patients for adjuvant therapy regimens. This study sought to determine the biological significance of RABL6A (RAB, member RAS oncogene family-like protein 6 isoform A), a novel pancreatic protein, in PDAC. Analyses of RABL6A protein expression in PDAC specimens from 73 patients who underwent pancreatic resection showed that RABL6A levels are altered in 74% of tumors relative to adjacent benign ductal epithelium. Undetectable RABL6A expression, found in 7% (5/73) of patients, correlated with improved overall survival (range 41 to 118 months with 3/5 patients still living), while patients with RABL6A expression had a worse outcome (range 3.3 to 100 months, median survival 20.3 months) (P = 0.0134). In agreement with those findings, RABL6A expression was increased in pancreatic cancer cell lines compared to normal pancreatic epithelial cells, and its knockdown inhibited pancreatic cancer cell proliferation and induced apoptosis. Moreover, RABL6A depletion selectively sensitized cells to oxaliplatin-induced arrest and death. This work reveals that RABL6A promotes the proliferation, survival, and oxaliplatin resistance of PDAC cells, whereas its loss is associated with extended survival in patients with resected PDAC. Such data suggest RABL6A is a novel biomarker of PDAC and potential target for anticancer therapy.
    Language English
    Publishing date 2013-10-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2538519-7
    ISSN 1947-6027 ; 1947-6019
    ISSN (online) 1947-6027
    ISSN 1947-6019
    DOI 10.1177/1947601913501074
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    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.

  6. Article ; Online: RABL6A promotes G1-S phase progression and pancreatic neuroendocrine tumor cell proliferation in an Rb1-dependent manner.

    Hagen, Jussara / Muniz, Viviane P / Falls, Kelly C / Reed, Sara M / Taghiyev, Agshin F / Quelle, Frederick W / Gourronc, Francoise A / Klingelhutz, Aloysius J / Major, Heather J / Askeland, Ryan W / Sherman, Scott K / O'Dorisio, Thomas M / Bellizzi, Andrew M / Howe, James R / Darbro, Benjamin W / Quelle, Dawn E

    Cancer research

    2014  Volume 74, Issue 22, Page(s) 6661–6670

    Abstract: Mechanisms of neuroendocrine tumor (NET) proliferation are poorly understood, and therapies that effectively control NET progression and metastatic disease are limited. We found amplification of a putative oncogene, RABL6A, in primary human pancreatic ... ...

    Abstract Mechanisms of neuroendocrine tumor (NET) proliferation are poorly understood, and therapies that effectively control NET progression and metastatic disease are limited. We found amplification of a putative oncogene, RABL6A, in primary human pancreatic NETs (PNET) that correlated with high-level RABL6A protein expression. Consistent with those results, stable silencing of RABL6A in cultured BON-1 PNET cells revealed that it is essential for their proliferation and survival. Cells lacking RABL6A predominantly arrested in G1 phase with a moderate mitotic block. Pathway analysis of microarray data suggested activation of the p53 and retinoblastoma (Rb1) tumor-suppressor pathways in the arrested cells. Loss of p53 had no effect on the RABL6A knockdown phenotype, indicating that RABL6A functions independent of p53 in this setting. By comparison, Rb1 inactivation partially restored G1 to S phase progression in RABL6A-knockdown cells, although it was insufficient to override the mitotic arrest and cell death caused by RABL6A loss. Thus, RABL6A promotes G1 progression in PNET cells by inactivating Rb1, an established suppressor of PNET proliferation and development. This work identifies RABL6A as a novel negative regulator of Rb1 that is essential for PNET proliferation and survival. We suggest RABL6A is a new potential biomarker and target for anticancer therapy in PNET patients.
    MeSH term(s) Cell Line, Tumor ; Cell Proliferation ; G1 Phase ; Humans ; Mitosis ; Neuroendocrine Tumors/pathology ; Oncogene Proteins/physiology ; Pancreatic Neoplasms/pathology ; Retinoblastoma Protein/physiology ; S Phase ; rab GTP-Binding Proteins/physiology
    Chemical Substances Oncogene Proteins ; Retinoblastoma Protein ; RABL6A protein, human (EC 3.6.1.-) ; rab GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2014-10-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-13-3742
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    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

    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.

To top