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, Darrell W Brann, R. R. Tekmal, R. K. Vadlamudi

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 - Jan 1 2014

Fingerprint

DNA Damage
Ataxia Telangiectasia
Camptothecin
p53 Genes
Etoposide
Cytoplasmic and Nuclear Receptors
Cell Cycle Checkpoints
human PELP1 protein
Neoplasms
Transcription Factors
Phosphotransferases
Phosphorylation
Radiation
Apoptosis
Breast Neoplasms
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Nair, B. C., Krishnan, S. R., Sareddy, G. R., Mann, M., Xu, B., Natarajan, M., ... 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

Proline, glutamic acid and leucine-rich protein-1 is essential for optimal p53-mediated DNA damage response. / Nair, B. C.; Krishnan, S. R.; Sareddy, G. R.; Mann, M.; Xu, B.; Natarajan, M.; Hasty, P.; Brann, Darrell W; Tekmal, R. R.; Vadlamudi, R. K.

In: Cell Death and Differentiation, Vol. 21, No. 9, 01.01.2014, p. 1409-1418.

Research output: Contribution to journalArticle

Nair, BC, Krishnan, SR, Sareddy, GR, Mann, M, Xu, B, Natarajan, M, Hasty, P, Brann, DW, Tekmal, RR & Vadlamudi, RK 2014, 'Proline, glutamic acid and leucine-rich protein-1 is essential for optimal p53-mediated DNA damage response', Cell Death and Differentiation, vol. 21, no. 9, pp. 1409-1418. https://doi.org/10.1038/cdd.2014.55
Nair, B. C. ; Krishnan, S. R. ; Sareddy, G. R. ; Mann, M. ; Xu, B. ; Natarajan, M. ; Hasty, P. ; Brann, Darrell W ; Tekmal, R. R. ; Vadlamudi, R. K. / Proline, glutamic acid and leucine-rich protein-1 is essential for optimal p53-mediated DNA damage response. In: Cell Death and Differentiation. 2014 ; Vol. 21, No. 9. pp. 1409-1418.
@article{4ae3ce23fe694f508b7457e6fa732157,
title = "Proline, glutamic acid and leucine-rich protein-1 is essential for optimal p53-mediated DNA damage response",
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.",
author = "Nair, {B. C.} and Krishnan, {S. R.} and Sareddy, {G. R.} and M. Mann and B. Xu and M. Natarajan and P. Hasty and Brann, {Darrell W} and Tekmal, {R. R.} and Vadlamudi, {R. K.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1038/cdd.2014.55",
language = "English (US)",
volume = "21",
pages = "1409--1418",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Nature Publishing Group",
number = "9",

}

TY - JOUR

T1 - Proline, glutamic acid and leucine-rich protein-1 is essential for optimal p53-mediated DNA damage response

AU - Nair, B. C.

AU - Krishnan, S. R.

AU - Sareddy, G. R.

AU - Mann, M.

AU - Xu, B.

AU - Natarajan, M.

AU - Hasty, P.

AU - Brann, Darrell W

AU - Tekmal, R. R.

AU - Vadlamudi, R. K.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84905921690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905921690&partnerID=8YFLogxK

U2 - 10.1038/cdd.2014.55

DO - 10.1038/cdd.2014.55

M3 - Article

VL - 21

SP - 1409

EP - 1418

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1350-9047

IS - 9

ER -