proline-, glutamic acid- & leucine-rich protein 1 (modulator of nongenomic activity of estrogen receptor, transcription factor HMX3, PELP1, HMX3, MNAR)
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Function
- coactivator of estrogen receptor-mediated transcription
- corepressor of other nuclear hormone receptors & sequence- specific transcription factors
- role in estrogen receptor (ER) genomic activity when resides in the nuclear compartment by activating the ER target genes
- facilitates ER nongenomic signaling via SRC & PI3K interaction in the cytosol
- role in E2-mediated cell cycle progression by interacting with RB1
- role in ER/growth factor cross-talk (putative)
- interacts with several growth factor signaling components including EGFR & HRS
- involved in nuclear receptor signaling via its interaction with AR & NR3C1
- interacts with HRS, RXRA, SUMO2, HDAC2, RB1 & STAT3
- interacts with PI3K, SRC & EGFR in cytoplas
- interacts with ESR1 & ESR2; interaction is enhanced by 17-beta-estradiol
- interacts with CREBBP, EP300, AR & NR3C1 (ligand-dependent)
- forms 2 complexes in presence of 17-beta-estradio
- interacts with histone H1 & H3, greater affinity for H1
- phosphorylated upon DNA damage, probably by ATM or ATR
Structure
- Glu-rich region mediates histones interaction
- LXXLL motifs are required for association with nuclear receptor ESR1
Compartment
- nucleus, cytoplasm
- also found in plasma membrane
Alternative splicing
named isoforms=2
Expression
- Isoform 1 is widely expressed
Pathology
- may promote tumorigenesis via its interaction with & modulation of several oncogenes including SRC, PI3K, STAT3 & EGFR
- role in cancer cell metastasis via its ability to modulate E2-mediated cytoskeleton changes & cell migration via its interaction with SRC & PI3K
- isoform 2 is expressed in breast cancer cell lines
- in a subset of breast tumors mainly in cytoplasm
- localization is widely deregulated in endometrial cancers with predominantly in cytoplasm of high-grade endometrial tumors