Tumor suppressors p53, p63TAα, p63TAy, p73α, and p73β use distinct pathways to repress telomerase expression.

J Biol Chem

Center for Viral Oncology and Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.

Published: June 2012

The promoter of the telomerase catalytic subunit (TERT) is subject to tight regulation and remains repressed in somatic cells to ensure their limited life span and to prevent tumor initiation. Here we report that the hTERT promoter is strongly repressed by p53 and the related family members p63 and p73. We found that p53-mediated repression was different in human and mouse cells and occurred through p53-dependent transcription inhibition of c-Myc or through E-box/E2F pathways, respectively. Although p63TAα-mediated repression occurred through SP1, p63TAy-mediated repression occurred through E2F signaling. Finally, p73α- and p73β-mediated repression occurred through NF-YB2. Our results show a complex multifactorial mechanism used by p53 and its family members to keep hTERT expression under tight control.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370256PMC
http://dx.doi.org/10.1074/jbc.M111.319236DOI Listing

Publication Analysis

Top Keywords

repression occurred
12
p53 family
8
family members
8
tumor suppressors
4
suppressors p53
4
p53 p63taα
4
p63taα p63tay
4
p63tay p73α
4
p73α p73β
4
p73β distinct
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!