Document Detail

JAZ mediates G1 cell-cycle arrest and apoptosis by positively regulating p53 transcriptional activity.
MedLine Citation:
PMID:  16931621     Owner:  NLM     Status:  MEDLINE    
We previously identified JAZ as a novel zinc finger (ZF) protein by screening a murine interleukin-3 (IL-3)-dependent NFS/N1.H7 myeloid cell cDNA library. JAZ is a member of a new class of ZFPs that is evolutionarily conserved and preferentially binds to dsRNA, but its function was unknown. Now, we report that the stress of IL-3 growth factor withdrawal up-regulates JAZ expression in hematopoietic cells in association with p53 activation and induction of cell death. Biochemical analysis reveals that JAZ associates with p53 to stimulate its transcriptional activity in p53-expressing cells, but not in p53-null cells unless complemented with p53. JAZ functions to mediate G1 cell-cycle arrest followed by apoptosis in a p53-dependent mechanism that is associated with up-regulation of p21 and BAX, dephosphorylation of Rb, and repression of cyclin A. Of importance, siRNA "knockdown" of endogenous JAZ inhibits p53 transcriptional activity, decreases the G1/G0 population, and attenuates stress-induced cell death. While JAZ directly binds p53 in vitro in a mechanism requiring p53's C-terminal regulatory domain but independent of dsRNA, the dsRNA-binding ZF domains are required for JAZ's stimulatory role of p53 in vivo by dictating its nuclear localization. Thus, JAZ is a novel negative regulator of cell growth by positively regulating p53.
Mingli Yang; Song Wu; Xuekun Su; W Stratford May
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-08-24
Journal Detail:
Title:  Blood     Volume:  108     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-06     Completed Date:  2007-01-17     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4136-45     Citation Subset:  AIM; IM    
University of Florida Shands Cancer Center, Department of Medicine, University of Florida, 1376 Mowry Rd, Gainesville, FL 32610-3633, USA.
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MeSH Terms
Active Transport, Cell Nucleus / drug effects,  genetics
Apoptosis / genetics*
Cell Line, Tumor
Cell Nucleus / genetics,  metabolism
Cyclin A / biosynthesis,  genetics
DNA-Binding Proteins / antagonists & inhibitors,  biosynthesis,  genetics*
G1 Phase / genetics*
Hematopoietic Stem Cells / metabolism
Interleukin-3 / immunology,  pharmacology
Protein Binding / drug effects,  genetics
Protein-Serine-Threonine Kinases / genetics,  metabolism
RNA, Small Interfering / genetics,  pharmacology
RNA-Binding Proteins / antagonists & inhibitors,  biosynthesis,  genetics*
Transcription, Genetic / drug effects,  genetics
Tumor Suppressor Protein p53 / biosynthesis,  genetics*
Up-Regulation / drug effects,  genetics*
bcl-2-Associated X Protein
p21-Activated Kinases
Grant Support
Reg. No./Substance:
0/Bax protein, mouse; 0/Cyclin A; 0/DNA-Binding Proteins; 0/Interleukin-3; 0/RNA, Small Interfering; 0/RNA-Binding Proteins; 0/Tumor Suppressor Protein p53; 0/Zfp346 protein, mouse; 0/bcl-2-Associated X Protein; EC Kinases; EC Kinases

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

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