Proline-, glutamate- and leucine-rich protein 1 (PELP1)

Proline-, glutamate- and leucine-rich protein 1 (PELP1) is a versatile scaffold protein and a coregulator for several nuclear receptors, including the estrogen receptor (ER), androgen receptor (AR), and glucocorticoid receptor (GR). It plays a pivotal role in integrating genomic and non-genomic signaling pathways, often acting as a bridge between nuclear receptors and cytoplasmic kinase cascades such as the MAPK and PI3K/Akt pathways (Source: UniProt Q8IZL8; PubMed: 25613340). PELP1 is frequently overexpressed in various cancers, where it promotes cell proliferation, survival, and metastasis, and is often associated with resistance to endocrine therapies (Source: PubMed: 30104349). Beyond its role in hormonal signaling, PELP1 is involved in chromatin remodeling through interactions with histones and is essential for ribosome biogenesis in the nucleolus (Source: PubMed: 21737453). Given its central role in oncogenic signaling hubs, PELP1 is considered a high-value therapeutic target, with research focusing on small molecule inhibitors and PROTACs to disrupt its pathological functions (Source: PubMed: 33452134).

Other names

Modulator of nongenomic activity of estrogen receptorMNARP160Transcription factor HRE-binding proteinHREBP

Disruption of PELP1 interaction with nuclear receptors (e.g., Estrogen Receptor) or other signaling molecules; targeted protein degradation.