LIVIVO - Search results -

Search results

Result 1 - 8 of total 8

Search options

Article ; Online: Splicing factor

Gökmen-Polar, Yesim / Neelamraju, Yaseswini / Goswami, Chirayu P / Gu, Yuan / Gu, Xiaoping / Nallamothu, Gouthami / Vieth, Edyta / Janga, Sarath C / Ryan, Michael / Badve, Sunil S

EMBO reports

2019 Volume 20, Issue 2

Abstract: The epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) control the epithelial-to-mesenchymal transition (EMT) splicing program in cancer. However, their role in breast cancer recurrence is unclear. In this study, we report that high levels ...

Abstract	The epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) control the epithelial-to-mesenchymal transition (EMT) splicing program in cancer. However, their role in breast cancer recurrence is unclear. In this study, we report that high levels of ESRP1, but not ESRP2, are associated with poor prognosis in estrogen receptor positive (ER+) breast tumors. Knockdown of ESRP1 in endocrine-resistant breast cancer models decreases growth significantly and alters the EMT splicing signature, which we confirm using TCGA SpliceSeq data of ER+ BRCA tumors. However, these changes are not accompanied by the development of a mesenchymal phenotype or a change in key EMT-transcription factors. In tamoxifen-resistant cells, knockdown of ESRP1 affects lipid metabolism and oxidoreductase processes, resulting in the decreased expression of fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1), and phosphoglycerate dehydrogenase (PHGDH) at both the mRNA and protein levels. Furthermore, ESRP1 knockdown increases the basal respiration and spare respiration capacity. This study reports a novel role for ESRP1 that could form the basis for the prevention of tamoxifen resistance in ER+ breast cancer.
MeSH term(s)	Alternative Splicing ; Antineoplastic Agents/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Energy Metabolism ; Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Metabolic Networks and Pathways ; Proportional Hazards Models ; RNA Splicing Factors/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Receptors, Estrogen/metabolism
Chemical Substances	Antineoplastic Agents ; ESRP1 protein, human ; RNA Splicing Factors ; RNA-Binding Proteins ; Receptors, Estrogen
Language	English
Publishing date	2019-01-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.15252/embr.201846078
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5433: 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 41: Show issues

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.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Developmental function of Nm23/awd: a mediator of endocytosis.

Nallamothu, Gouthami / Dammai, Vincent / Hsu, Tien

Molecular and cellular biochemistry

2009 Volume 329, Issue 1-2, Page(s) 35–44

Abstract: The metastasis suppressor gene Nm23 is highly conserved from yeast to human, implicating a critical developmental function. Studies in cultured mammalian cells have identified several potential functions, but many have not been directly verified in vivo. ...

Abstract	The metastasis suppressor gene Nm23 is highly conserved from yeast to human, implicating a critical developmental function. Studies in cultured mammalian cells have identified several potential functions, but many have not been directly verified in vivo. Here, we summarize the studies on the Drosophila homolog of the Nm23 gene, named a bnormal w ing d iscs (awd), which shares 78% amino acid identity with the human Nm23-H1 and H2 isoforms. These studies confirmed that awd gene encodes a nucleoside diphosphate kinase, and provided strong evidence of a role for awd in regulating cell differentiation and motility via regulation of growth factor receptor signaling. The latter function is mainly mediated by control of endocytosis. This review provides a historical account of the discovery and subsequent analyses of the awd gene. We will also discuss the possible molecular function of the Awd protein that underlies the endocytic function.
MeSH term(s)	Amino Acid Sequence ; Animals ; Drosophila/embryology ; Drosophila/genetics ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Embryo, Nonmammalian ; Endocytosis/genetics ; Endocytosis/physiology ; Gene Expression Regulation, Developmental ; Genes, Insect ; Humans ; Molecular Sequence Data ; NM23 Nucleoside Diphosphate Kinases/genetics ; NM23 Nucleoside Diphosphate Kinases/metabolism ; Nucleoside-Diphosphate Kinase/genetics ; Nucleoside-Diphosphate Kinase/metabolism ; Sequence Homology, Amino Acid
Chemical Substances	Drosophila Proteins ; NM23 Nucleoside Diphosphate Kinases ; Nucleoside-Diphosphate Kinase (EC 2.7.4.6) ; awd protein, Drosophila (EC 2.7.4.6)
Language	English
Publishing date	2009-04-17
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-009-0112-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 892: 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 ▾

Article: Developmental function of Nm23/awd: a mediator of endocytosis

Nallamothu, Gouthami / Dammai, Vincent / Hsu, Tien

Molecular and cellular biochemistry. 2009 Sept., v. 329, no. 1-2

2009

Abstract	The metastasis suppressor gene Nm23 is highly conserved from yeast to human, implicating a critical developmental function. Studies in cultured mammalian cells have identified several potential functions, but many have not been directly verified in vivo. Here, we summarize the studies on the Drosophila homolog of the Nm23 gene, named a bnormal w ing d iscs (awd), which shares 78% amino acid identity with the human Nm23-H1 and H2 isoforms. These studies confirmed that awd gene encodes a nucleoside diphosphate kinase, and provided strong evidence of a role for awd in regulating cell differentiation and motility via regulation of growth factor receptor signaling. The latter function is mainly mediated by control of endocytosis. This review provides a historical account of the discovery and subsequent analyses of the awd gene. We will also discuss the possible molecular function of the Awd protein that underlies the endocytic function.
Language	English
Dates of publication	2009-09
Size	p. 35-44.
Publisher	Springer US
Publishing place	Boston
Document type	Article
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-009-0112-7
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 74/721: Show issues

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.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The Drosophila metastasis suppressor gene Nm23 homolog, awd, regulates epithelial integrity during oogenesis.

Woolworth, Julie A / Nallamothu, Gouthami / Hsu, Tien

Molecular and cellular biology

2009 Volume 29, Issue 17, Page(s) 4679–4690

Abstract: The expression levels of the metastasis suppressor gene Nm23 have been shown to correlate positively or inversely with prognosis in different cancer cohorts. This indicates that Nm23 may be needed at different expression levels and may function ... ...

Abstract	The expression levels of the metastasis suppressor gene Nm23 have been shown to correlate positively or inversely with prognosis in different cancer cohorts. This indicates that Nm23 may be needed at different expression levels and may function differently in various tissues. Here we report a novel epithelial function of the Drosophila melanogaster homolog of human Nm23, abnormal wing discs (awd). We show a dynamic expression pattern of the Awd protein during morphogenesis of the Drosophila follicle cells during oogenesis. Loss-of-function awd mutant cells result in the accumulation and spreading of adherens junction components, such as Drosophila E-cadherin, beta-catenin/Armadillo, and alpha-spectrin, and the disruption of epithelial integrity, including breaking up of the epithelial sheet and piling up of follicle cells. In contrast, overexpression of awd diminishes adherens junction components and induces a mesenchymal-cell-like cell shape change. The gain-of-function phenotype is consistent with a potential oncogenic function of this metastasis suppressor gene. Interestingly, we demonstrate that the epithelial function of awd is mediated by Rab5 and show that the Rab5 expression level is downregulated in awd mutant cells. Therefore, awd modulates the level and localization of adherens junction components via endocytosis. This is the first demonstration of an in vivo function of Nm23 family genes in regulating epithelial morphogenesis.
MeSH term(s)	Adherens Junctions/metabolism ; Animals ; Animals, Genetically Modified ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/anatomy & histology ; Drosophila melanogaster/embryology ; Drosophila melanogaster/physiology ; Epithelium/anatomy & histology ; Epithelium/embryology ; Female ; Genes, Tumor Suppressor ; Humans ; Morphogenesis/physiology ; Nucleoside-Diphosphate Kinase/genetics ; Nucleoside-Diphosphate Kinase/metabolism ; Oogenesis/physiology ; Ovary/anatomy & histology ; Ovary/metabolism ; Phenotype ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; rab5 GTP-Binding Proteins/genetics ; rab5 GTP-Binding Proteins/metabolism
Chemical Substances	Drosophila Proteins ; Recombinant Fusion Proteins ; Nucleoside-Diphosphate Kinase (EC 2.7.4.6) ; awd protein, Drosophila (EC 2.7.4.6) ; rab5 GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2009-07-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.00297-09
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1666: 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 ; Online: Notch signaling during development requires the function of awd, the Drosophila homolog of human metastasis suppressor gene Nm23.

Ignesti, Marilena / Barraco, Marilena / Nallamothu, Gouthami / Woolworth, Julie A / Duchi, Serena / Gargiulo, Giuseppe / Cavaliere, Valeria / Hsu, Tien

BMC biology

2014 Volume 12, Page(s) 12

Abstract: Background: The Drosophila abnormal wing discs (awd) belongs to a highly conserved family of genes implicated in metastasis suppression, metabolic homeostasis and epithelial morphogenesis. The cellular function of the mammalian members of this family, ... ...

Abstract	Background: The Drosophila abnormal wing discs (awd) belongs to a highly conserved family of genes implicated in metastasis suppression, metabolic homeostasis and epithelial morphogenesis. The cellular function of the mammalian members of this family, the Nm23 proteins, has not yet been clearly defined. Previous awd genetic analyses unraveled its endocytic role that is required for proper internalization of receptors controlling different signaling pathways. In this study, we analyzed the role of Awd in controlling Notch signaling during development. Results: To study the awd gene function we used genetic mosaic approaches to obtain cells homozygous for a loss of function allele. In awd mutant follicle cells and wing disc cells, Notch accumulates in enlarged early endosomes, resulting in defective Notch signaling. Our results demonstrate that awd function is required before γ-secretase mediated cleavage since over-expression of the constitutively active form of the Notch receptor in awd mutant follicle cells allows rescue of the signaling. By using markers of different endosomal compartments we show that Notch receptor accumulates in early endosomes in awd mutant follicle cells. A trafficking assay in living wing discs also shows that Notch accumulates in early endosomes. Importantly, constitutively active Rab5 cannot rescue the awd phenotype, suggesting that awd is required for Rab5 function in early endosome maturation. Conclusions: In this report we demonstrate that awd is essential for Notch signaling via its endocytic role. In addition, we identify the endocytic step at which Awd function is required for Notch signaling and we obtain evidence indicating that Awd is necessary for Rab5 function. These findings provide new insights into the developmental and pathophysiological function of this important gene family.
MeSH term(s)	Animals ; Cell Proliferation ; Clone Cells ; Cytoplasmic Vesicles ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/growth & development ; Drosophila melanogaster/metabolism ; Endocytosis ; Endosomes/metabolism ; Female ; Gene Expression Regulation, Developmental ; Humans ; Imaginal Discs/cytology ; Larva/growth & development ; Larva/metabolism ; Mutation/genetics ; NM23 Nucleoside Diphosphate Kinases/genetics ; NM23 Nucleoside Diphosphate Kinases/metabolism ; Neoplasm Metastasis ; Nucleoside-Diphosphate Kinase/metabolism ; Ovarian Follicle/cytology ; Ovarian Follicle/metabolism ; Protein Transport ; Receptors, Notch/metabolism ; Sequence Homology, Amino Acid ; Signal Transduction ; Wings, Animal/cytology ; Wings, Animal/metabolism ; rab5 GTP-Binding Proteins/metabolism
Chemical Substances	Drosophila Proteins ; N protein, Drosophila ; NM23 Nucleoside Diphosphate Kinases ; Receptors, Notch ; NME1 protein, human (EC 2.7.4.6) ; Nucleoside-Diphosphate Kinase (EC 2.7.4.6) ; awd protein, Drosophila (EC 2.7.4.6) ; Rab5 protein, Drosophila (EC 3.6.1.47.) ; rab5 GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2014-02-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2133020-7
ISSN	1741-7007 ; 1741-7007
ISSN (online)	1741-7007
ISSN	1741-7007
DOI	10.1186/1741-7007-12-12
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Expression levels of SF3B3 correlate with prognosis and endocrine resistance in estrogen receptor-positive breast cancer.

Gökmen-Polar, Yesim / Neelamraju, Yaseswini / Goswami, Chirayu P / Gu, Xiaoping / Nallamothu, Gouthami / Janga, Sarath Chandra / Badve, Sunil

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2014 Volume 28, Issue 5, Page(s) 677–685

Abstract: De novo or acquired resistance to endocrine therapy limits its utility in a significant number of estrogen receptor-positive (ER-positive) breast cancers. It is crucial to identify novel targets for therapeutic intervention and improve the success of ... ...

Abstract	De novo or acquired resistance to endocrine therapy limits its utility in a significant number of estrogen receptor-positive (ER-positive) breast cancers. It is crucial to identify novel targets for therapeutic intervention and improve the success of endocrine therapies. Splicing factor 3b, subunit 1 (SF3B1) mutations are described in luminal breast cancer albeit in low frequency. In this study, we evaluated the role of SF3B1 and SF3B3, critical parts of the SF3b splicing complex, in ER-positive endocrine resistance. To ascertain the role of SF3B1/SF3B3 in endocrine resistance, their expression levels were evaluated in ER-positive/endocrine-resistant cell lines (MCF-7/LCC2 and MCF-7/LCC9) using a real-time quantitative reverse transcription PCR (qRT-PCR). To further determine their clinical relevance, expression analysis was performed in a cohort of 60 paraffin-embedded ER-positive, node-negative breast carcinomas with low, intermediate, and high Oncotype DX recurrence scores. Expression levels of SF3B1 and SF3B3 and their prognostic value were validated in large cohorts using publicly available gene expression data sets including The Cancer Genome Atlas. SF3B1 and SF3B3 levels were significantly increased in ERα-positive cells with acquired tamoxifen (MCF-7/LCC2; both P<0.0002) and fulvestrant/tamoxifen resistance (MCF-7/LCC9; P=0.008 for SF3B1 and P=0.0006 for SF3B3). Expression levels of both MCF-7/LCC2 and MCF-7/LCC9 were not affected by additional treatments with E2 and/or tamoxifen. Furthermore, qRT-PCR analysis confirmed that SF3B3 expression is significantly upregulated in Oncotype DX high-risk groups when compared with low risk (P=0.019). Similarly, in publicly available breast cancer gene expression data sets, overexpression of SF3B3, but not SF3B1, was significantly correlated with overall survival. Furthermore, the correlation was significant in ER-positive, but not in ER-negative tumors.This is the first study to document the role of SF3B3 in endocrine resistance and prognosis in ER-positive breast cancer. Potential strategies for therapeutic targeting of the splicing mechanism(s) need to be evaluated.
MeSH term(s)	Antineoplastic Agents, Hormonal/therapeutic use ; Biomarkers, Tumor/analysis ; Breast Neoplasms/metabolism ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology ; Drug Resistance, Neoplasm/physiology ; Estrogen Receptor alpha/biosynthesis ; Female ; Humans ; Kaplan-Meier Estimate ; Neoplasm Recurrence, Local/metabolism ; Neoplasm Recurrence, Local/mortality ; Neoplasm Recurrence, Local/pathology ; Polymerase Chain Reaction ; Prognosis ; RNA Splicing Factors ; RNA-Binding Proteins/biosynthesis ; Transcriptome ; Up-Regulation
Chemical Substances	Antineoplastic Agents, Hormonal ; Biomarkers, Tumor ; ESR1 protein, human ; Estrogen Receptor alpha ; RNA Splicing Factors ; RNA-Binding Proteins ; SF3B3 protein, human
Language	English
Publishing date	2014-11-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1038/modpathol.2014.146
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2450: 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

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Awd, the homolog of metastasis suppressor gene Nm23, regulates Drosophila epithelial cell invasion.

Nallamothu, Gouthami / Woolworth, Julie A / Dammai, Vincent / Hsu, Tien

Molecular and cellular biology

2008 Volume 28, Issue 6, Page(s) 1964–1973

Abstract: Border cell migration during Drosophila melanogaster oogenesis is a highly pliable model for studying epithelial to mesenchymal transition and directional cell migration. The process involves delamination of a group of 6 to 10 follicle cells from the ... ...

Abstract	Border cell migration during Drosophila melanogaster oogenesis is a highly pliable model for studying epithelial to mesenchymal transition and directional cell migration. The process involves delamination of a group of 6 to 10 follicle cells from the epithelium followed by guided migration and invasion through the nurse cell complex toward the oocyte. The guidance cue is mainly provided by the homolog of platelet-derived growth factor/vascular endothelial growth factor family of growth factor, or Pvf, emanating from the oocyte, although Drosophila epidermal growth factor receptor signaling also plays an auxiliary role. Earlier studies implicated a stringent control of the strength of Pvf-mediated signaling since both down-regulation of Pvf and overexpression of active Pvf receptor (Pvr) resulted in stalled border cell migration. Here we show that the metastasis suppressor gene homolog Nm23/awd is a negative regulator of border cell migration. Its down-regulation allows for optimal spatial signaling from two crucial pathways, Pvr and JAK/STAT. Its overexpression in the border cells results in stalled migration and can revert the phenotype of overexpressing constitutive Pvr or dominant-negative dynamin. This is a rare example demonstrating the relevance of a metastasis suppressor gene function utilized in a developmental process involving cell invasion.
MeSH term(s)	Animals ; Animals, Genetically Modified ; Cell Movement ; Down-Regulation ; Drosophila Proteins/biosynthesis ; Drosophila Proteins/deficiency ; Drosophila Proteins/genetics ; Drosophila Proteins/physiology ; Dynamins/deficiency ; Dynamins/genetics ; Dynamins/physiology ; Endocytosis ; Epithelial Cells/physiology ; Female ; Gene Expression Regulation, Developmental ; MAP Kinase Signaling System/physiology ; Nucleoside-Diphosphate Kinase/biosynthesis ; Nucleoside-Diphosphate Kinase/deficiency ; Nucleoside-Diphosphate Kinase/genetics ; Nucleoside-Diphosphate Kinase/physiology ; Ovary/cytology ; Promoter Regions, Genetic ; Receptor Protein-Tyrosine Kinases/physiology ; Receptors, Interleukin/genetics ; Receptors, Interleukin/physiology ; Recombinant Fusion Proteins/physiology ; Signal Transduction/physiology
Chemical Substances	Drosophila Proteins ; Receptors, Interleukin ; Recombinant Fusion Proteins ; dome protein, Drosophila ; Pvr protein, Drosophila (EC 2.7.10.1) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Nucleoside-Diphosphate Kinase (EC 2.7.4.6) ; awd protein, Drosophila (EC 2.7.4.6) ; Dynamins (EC 3.6.5.5) ; shi protein, Drosophila (EC 3.6.5.5)
Language	English
Publishing date	2008-01-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.01743-07
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1666: 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 ; Online: Drosophila von Hippel-Lindau tumor suppressor gene function in epithelial tubule morphogenesis.

Hsouna, Anita / Nallamothu, Gouthami / Kose, Nurgun / Guinea, Maria / Dammai, Vincent / Hsu, Tien

Molecular and cellular biology

2010 Volume 30, Issue 15, Page(s) 3779–3794

Abstract: Mutations in the human von Hippel-Lindau (VHL) gene are the cause of VHL disease that displays multiple benign and malignant tumors. The VHL gene has been shown to regulate angiogenic potential and glycolic metabolism via its E3 ubiquitin ligase function ...

Abstract	Mutations in the human von Hippel-Lindau (VHL) gene are the cause of VHL disease that displays multiple benign and malignant tumors. The VHL gene has been shown to regulate angiogenic potential and glycolic metabolism via its E3 ubiquitin ligase function against the alpha subunit of hypoxia-inducible factor (HIF-alpha). However, many HIF-independent functions of VHL have been identified. Recent evidence also indicates that the canonical function cannot fully explain the VHL mutant cell phenotypes, although it is still unclear how many of these noncanonical functions relate to the pathophysiological processes because of a lack of tractable genetic systems. Here, we report the first genomic mutant phenotype of Drosophila melanogaster VHL (dVHL) in the epithelial tubule network, the trachea, and show that dVHL regulates branch migration and lumen formation via its endocytic function. The endocytic function regulates the surface level of the chemotactic signaling receptor Breathless and promotes clearing of the lumen matrix during maturation of the tracheal tubes. Importantly, the regulatory function in tubular morphogenesis is conserved in the mammalian system, as conditional knockout of Vhl in mouse kidney also resulted in similar cell motility and lumen phenotypes.
MeSH term(s)	Animals ; Animals, Genetically Modified ; Cell Movement/genetics ; Drosophila/genetics ; Drosophila/metabolism ; Embryo, Mammalian ; Embryo, Nonmammalian ; Genes ; Humans ; Kidney/metabolism ; Mice ; Morphogenesis/genetics ; Mutation ; Phenotype ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Von Hippel-Lindau Tumor Suppressor Protein ; von Hippel-Lindau Disease/genetics ; von Hippel-Lindau Disease/metabolism
Chemical Substances	Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Von Hippel-Lindau Tumor Suppressor Protein (EC 2.3.2.27) ; VHL protein, human (EC 6.3.2.-)
Language	English
Publishing date	2010-06-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.01578-09
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1666: 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

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Bonn / Germany

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