GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:17719541

From GONUTS
Jump to: navigation, search
Citation

Das, S, Raj, L, Zhao, B, Kimura, Y, Bernstein, A, Aaronson, SA and Lee, SW (2007) Hzf Determines cell survival upon genotoxic stress by modulating p53 transactivation. Cell 130:624-37

Abstract

A critical unresolved issue about the genotoxic stress response is how the resulting activation of the p53 tumor suppressor can lead either to cell-cycle arrest and DNA repair or to apoptosis. We show here that hematopoietic zinc finger (Hzf), a zinc-finger-containing p53 target gene, modulates p53 transactivation functions in an autoregulatory feedback loop. Hzf is induced by p53 and binds to its DNA-binding domain, resulting in preferential transactivation of proarrest p53 target genes over its proapoptotic target genes. Thus, p53 activation results in cell-cycle arrest in Hzf wild-type MEFs, while in Hzf(-/-) MEFs, apoptosis is induced. Exposure of Hzf null mice to ionizing radiation resulted in enhanced apoptosis in several organs, as compared to in wild-type mice. These findings provide novel insights into the regulation of p53 transactivation function and suggest that Hzf functions as a key player in regulating cell fate decisions in response to genotoxic stress.

Links

PubMed PMC2779720 Online version:10.1016/j.cell.2007.06.013

Keywords

Animals; Apoptosis/genetics; Apoptosis/radiation effects; Cell Culture Techniques; Cell Line, Tumor; Cell Survival; DNA Damage; Feedback, Physiological; Female; Gamma Rays; Glutathione Transferase/metabolism; HCT116 Cells; Humans; Immunohistochemistry; Male; Mice; Models, Biological; Osteosarcoma/pathology; Prostatic Neoplasms/pathology; Proteins/genetics; Proteins/metabolism; RNA, Small Interfering; Recombinant Proteins/metabolism; Transcriptional Activation; Tumor Suppressor Protein p53/genetics; Tumor Suppressor Protein p53/metabolism; Two-Hybrid System Techniques; Whole-Body Irradiation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:P53

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96PM9

F

Seeded From UniProt

complete

MOUSE:Z385A

involved_in

GO:0006974: cellular response to DNA damage stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:Z385A

involved_in

GO:0006915: apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:Z385A

colocalizes_with

GO:0000785: chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:Z385A

enables

GO:0002039: p53 binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P04637

F

Seeded From UniProt

complete

HUMAN:Z385A

involved_in

GO:1902166: negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:Z385A

involved_in

GO:1902164: positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.