Proline, glutamic acid and leucine-rich protein-1 is essential for optimal p53-mediated DNA damage response.
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.
University of Texas Health Science Center, and Cancer Therapy and Research Center, San Antonio, TX, USA.
B C
BC
Nair
University of Texas Health Science Center, and Cancer Therapy and Research Center, San Antonio, TX, USA.
S R
SR
Krishnan
University of Texas Health Science Center, and Cancer Therapy and Research Center, San Antonio, TX, USA.
G R
GR
Sareddy
University of Texas Health Science Center, and Cancer Therapy and Research Center, San Antonio, TX, USA.
M
M
Mann
Molecular Radiation Biology Laboratory, Research Institute, South Birmingham, AL, USA.
B
B
Xu
University of Texas Health Science Center, and Cancer Therapy and Research Center, San Antonio, TX, USA.
M
M
Natarajan
University of Texas Health Science Center, and Cancer Therapy and Research Center, San Antonio, TX, USA.
P
P
Hasty
Institute of Molecular Medicine and Genetics, Georgia Reagents University, Augusta, GA, USA.
D
D
Brann
University of Texas Health Science Center, and Cancer Therapy and Research Center, San Antonio, TX, USA.
R R
RR
Tekmal
University of Texas Health Science Center, and Cancer Therapy and Research Center, San Antonio, TX, USA.
R K
RK
Vadlamudi
D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins / Q000378:metabolism*; D004249:DNA Damage; D006801:Humans; D061986:MCF-7 Cells; D010766:Phosphorylation; D014157:Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D056970:Co-Repressor Proteins; C438485:PELP1 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53