GSBS Student Publications

Title

hHR23B is required for genotoxic-specific activation of p53 and apoptosis

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cancer Biology; Department of Medicine, Division of Hematology/Oncology

Date

8-23-2006

Document Type

Article

Medical Subject Headings

*Apoptosis; Chromatin; Chromatin Immunoprecipitation; DNA; *DNA Damage; DNA Repair Enzymes; DNA-Binding Proteins; Humans; Lysine; Mutation; Promoter Regions (Genetics); Proto-Oncogene Proteins p21(ras); RNA Interference; Tumor Suppressor Protein p53; Ubiquitin

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Rad23 proteins function in both DNA repair and protein stability regulation. As ubiquitinated forms of p53 are stabilized after DNA damage in concert with p53 functional activation, and human Rad23 proteins (hHR23A and B) regulate p53 stability in unstressed cells, the role of hHR23B in post-genotoxin regulation of p53 was investigated. Depletion of hHR23B by specific short interfering RNA before genotoxic exposure attenuated p53, p21 and bax induction, abrogated the accumulation of ubiquitinated p53 and suppressed apoptosis. Expression of ubiquitin derivatives with all lysines mutated except K48 or K63 demonstrated that K48-linked p53-ubiquitin conjugates were specifically induced after DNA damage. hHR23B, along with native and ubiquitinated p53, accumulated in chromatin after genotoxic exposure, and the accumulation of ubiquitinated p53 in chromatin was prevented by hHR23B depletion. Chromatin immunoprecipitation analysis demonstrated that hHR23B and p53 both localized to the p21 promoter shortly after DNA damage. hHR23B thus plays a critical role in the activation and function of p53 after specific genotoxic exposures.

Rights and Permissions

Citation: Oncogene. 2007 Feb 22;26(8):1231-7. Epub 2006 Aug 21. Link to article on publisher's site

DOI of Published Version

10.1038/sj.onc.1209865

Related Resources

Link to article in PubMed

Journal Title

Oncogene

PubMed ID

16924240