RRC ID 45084
Author Kasim V, Huang C, Zhang J, Jia H, Wang Y, Yang L, Miyagishi M, Wu S.
Title Synergistic cooperation of MDM2 and E2F1 contributes to TAp73 transcriptional activity.
Journal Biochem Biophys Res Commun
Abstract TAp73, a structural homologue of p53, plays an important role in tumorigenesis. E2F1 had been reported as a transcriptional regulator of TAp73, however, the detailed mechanism remains to be elucidated. Here we reported that MDM2-silencing reduced the activities of the TAp73 promoters and the endogenous TAp73 expression level significantly; while MDM2 overexpression upregulated them. We further revealed that the regulation of TAp73 transcriptional activity occurs as a synergistic effect of MDM2 and E2F1, most probably through their physical interaction in the nuclei. Furthermore, we also suggested that MDM2 might be involved in DNA damage-induced TAp73 transcriptional activity. Finally, we elucidated that MDM2-silencing reduced the proliferation rate of colon carcinoma cells regardless of the p53 status. Our data show a synergistic effect of MDM2 and E2F1 on TAp73 transcriptional activity, suggesting a novel regulation pathway of TAp73.
Volume 449(3)
Pages 319-26
Published 2014-7-4
DOI 10.1016/j.bbrc.2014.05.026
PII S0006-291X(14)00880-8
PMID 24845566
MeSH Cell Line, Tumor Cell Proliferation DNA-Binding Proteins / metabolism* E2F1 Transcription Factor / metabolism* HEK293 Cells Humans Nuclear Proteins / metabolism* Promoter Regions, Genetic Proto-Oncogene Proteins c-mdm2 / genetics Proto-Oncogene Proteins c-mdm2 / metabolism* Transcription, Genetic* Transcriptional Activation* Tumor Protein p73 Tumor Suppressor Proteins / metabolism*
IF 2.985
Times Cited 2
WOS Category BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells 293T(RCB2202)