Document Detail


Three-amino-acid-loop-extension homeodomain factor Meis3 regulates cell survival via PDK1.
MedLine Citation:
PMID:  21059917     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Three-amino-acid-loop-extension (TALE) homeodomain proteins including Meis and Pbx families are generally recognized for their roles in growth and differentiation during vertebrate embryogenesis and tumorigenesis. Whereas genetic studies indicate that Pbx1 regulates the development and function of insulin-producing pancreatic β-cells, the role of Meis family members in β-cells is still unknown. Here we show that Meis3 is abundantly expressed in pancreatic islets and β-cells and that it regulates β-cell survival. We further identify the 3-phosphoinositide-dependent protein kinase 1 (PDK1), a well-known kinase involved in the PI3K-Akt signaling pathway, as a direct Meis3 target, which mediates its role in β-cell survival. This regulatory module appears to function broadly as we also identify Meis3 regulation of cell survival and PDK1 expression in ovarian carcinoma cells, suggesting a unique function for Meis3 beyond the traditional roles for TALE homeodomain factors during embryogenesis.
Authors:
Jiangying Liu; You Wang; Morris J Birnbaum; Doris A Stoffers
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-11-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  107     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-01-20     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  20494-9     Citation Subset:  IM    
Affiliation:
Institute for Diabetes, Obesity, and Metabolism and the Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / genetics*,  physiology
Blotting, Western
Cell Line, Tumor
Cell Survival / genetics,  physiology
Chromatin Immunoprecipitation
DNA Primers / genetics
Homeodomain Proteins / genetics,  metabolism*
In Situ Nick-End Labeling
Islets of Langerhans / metabolism*
Male
Mice
Mice, Inbred C57BL
Microarray Analysis
Protein-Serine-Threonine Kinases / genetics,  metabolism*
RNA, Small Interfering / genetics
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
P01 DK049210/DK/NIDDK NIH HHS; P30DK19525/DK/NIDDK NIH HHS; P30DK50306/DK/NIDDK NIH HHS; R01 DK068157/DK/NIDDK NIH HHS; R01 DK068157/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Homeodomain Proteins; 0/Meis3 protein, mouse; 0/RNA, Small Interfering; 0/Transcription Factors; EC 2.7.1.-/3-phosphoinositide-dependent protein kinase; EC 2.7.11.1/Protein-Serine-Threonine Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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