Proline, glutamic acid and leucine-rich protein-1 is essential for optimal p53-mediated DNA damage response

B. C. Nair, S. R. Krishnan, G. R. Sareddy, M. Mann, B. Xu, M. Natarajan, P. Hasty, D. Brann, R. R. Tekmal, R. K. Vadlamudi

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Proline-, glutamic acid- and leucine-rich protein-1 (PELP1) is a scaffolding oncogenic protein that functions as a coregulator for a number of nuclear receptors. p53 is an important transcription factor and tumor suppressor that has a critical role in DNA damage response (DDR) including cell cycle arrest, repair or apoptosis. In this study, we found an unexpected role for PELP1 in modulating p53-mediated DDR. PELP1 is phosphorylated at Serine1033 by various DDR kinases like ataxia-telangiectasia mutated, ataxia telangiectasia and Rad3-related or DNAPKc and this phosphorylation of PELP1 is important for p53 coactivation functions. PELP1-depleted p53 (wild-type) breast cancer cells were less sensitive to various genotoxic agents including etoposide, camptothecin or γ-radiation. PELP1 interacts with p53, functions as p53-coactivator and is required for optimal activation of p53 target genes under genomic stress. Overall, these studies established a new role of PELP1 in DDRs and these findings will have future implications in our understanding of PELP1's role in cancer progression.

Original languageEnglish (US)
Pages (from-to)1409-1418
Number of pages10
JournalCell Death and Differentiation
Volume21
Issue number9
DOIs
StatePublished - Sep 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Nair, B. C., Krishnan, S. R., Sareddy, G. R., Mann, M., Xu, B., Natarajan, M., Hasty, P., Brann, D., Tekmal, R. R., & Vadlamudi, R. K. (2014). Proline, glutamic acid and leucine-rich protein-1 is essential for optimal p53-mediated DNA damage response. Cell Death and Differentiation, 21(9), 1409-1418. https://doi.org/10.1038/cdd.2014.55