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) |