PELP1
Description
The PELP1 (proline, glutamate and leucine rich protein 1) is a protein-coding gene located on chromosome 17.
Proline-, glutamic acid- and leucine-rich protein 1 (PELP1), also known as modulator of non-genomic activity of estrogen receptor (MNAR) and transcription factor HMX3, is a protein encoded by the PELP1 gene in humans. It functions as a transcriptional corepressor for nuclear receptors like glucocorticoid receptors and a coactivator for estrogen receptors. PELP1 is a transcription coregulator that modulates the functions of several hormonal receptors and transcription factors. It plays essential roles in hormonal signaling, cell cycle progression, and ribosomal biogenesis. PELP1 expression is upregulated in several cancers, and its deregulation contributes to hormonal therapy resistance and metastasis, making it a potential therapeutic target for various cancers.
PELP1 is located on chromosome 17p13.2 and is expressed in a wide range of tissues, with the highest expression levels found in the brain, testes, ovaries, and uterus. There are two known isoforms (long 3.8 Kb and short 3.4 Kb), with the short isoform being widely expressed in cancer cells.
The PELP1 protein is 1130 amino acids long and exhibits both cytoplasmic and nuclear localization depending on the tissue. It lacks known enzymatic activity and functions as a scaffolding protein. PELP1 contains 10 NR-interacting boxes (LXXLL motifs) and acts as a coregulator of several nuclear receptors via these motifs, including ESR1, ESR2, ERR-alpha, PR, GR, AR, and RXR. It also functions as a coregulator of several other transcription factors, including AP1, SP1, NFkB, STAT3, and FHL2.
PELP1 acts as a coactivator for estrogen receptor-mediated transcription and a corepressor for other nuclear hormone receptors and sequence-specific transcription factors. It plays a role in estrogen receptor (ER) genomic activity by activating ER target genes in a hormonal stimulation-dependent manner. PELP1 can facilitate ER non-genomic signaling through interaction with SRC and PI3K in the cytosol. It participates in E2-mediated cell cycle progression by interacting with RB1. PELP1 may have important functional implications in ER/growth factor cross-talk and interacts with several growth factor signaling components, including EGFR and HRS. It serves as the key stabilizing component of the Five Friends of Methylated CHTOP (5FMC) complex, which is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. PELP1 is a component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit. It regulates pre-60S association of the critical remodeling factor MDN1. PELP1 may promote tumorigenesis through its interaction with and modulation of several oncogenes, including SRC, PI3K, STAT3, and EGFR. It plays a role in cancer cell metastasis by modulating E2-mediated cytoskeleton changes and cell migration through its interaction with SRC and PI3K.
PELP1 is also known as MNAR, P160.
