Molecular cloning and characterization of PELP1, a novel human coregulator of estrogen receptor alpha.
Nuclear hormone receptors (NRs) are transcription factors whose activity is regulated by ligands and by coactivators or corepressors. We report the characterization of a new NR coregulator: proline-, glutamic acid-, leucine-rich protein 1 (PELP1), a novel human protein that comprises 1,282 amino acids and is localized on chromosome 17. The primary structure of PELP1 consists of several motifs present in most transcriptional regulators including nine NR-interacting boxes (LXXLL motifs), a zinc finger, and glutamic acid- and proline-rich regions. We demonstrate that PELP1 is a coactivator of estrogen receptor alpha (ERalpha). PELP1 enhances 17beta-estradiol-dependent transcriptional activation from the estrogen response element in a dose-dependent manner. PELP1 interacts with ERalpha and also with general transcriptional coactivators p300 and cAMP response element-binding protein-binding protein. PELP1 was differentially expressed in various human and murine tissues with the highest expression levels in the testes, mammary glands, and brain. We also provide evidence supporting the developmental regulation of PELP1 expression in murine mammary glands, the detectable expression of PELP1 in human mammary cancer cell lines, and the enhanced expression of PELP1 in human breast tumors. These findings suggest that PELP1 is a novel coregulator of ERalpha and may have a role in breast cancer tumorigenesis.
Vadlamudi
R K
RK
University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. rvadlamu@mdanderson.org
Wang
R A
RA
Mazumdar
A
A
Kim
Y
Y
Shin
J
J
Sahin
A
A
Kumar
R
R
D000595:Amino Acid Sequence; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003001:Cloning, Molecular; D056970:Co-Repressor Proteins; D018076:DNA, Complementary; D047628:Estrogen Receptor alpha; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D056970:Co-Repressor Proteins; D018076:DNA, Complementary; D047628:Estrogen Receptor alpha; C438485:PELP1 protein, human; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors