Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1)

Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a transcriptional coregulator and scaffolding protein encoded by the PELP1 gene on chromosome 17p13.2. It modulates the activity of several nuclear receptors (notably estrogen, androgen, glucocorticoid, and progesterone receptors) and transcription factors (such as AP1, SP1, NFκB, STAT3, E2F1, and p53), mainly via its ten LXXLL motifs. PELP1 participates in hormonal signaling, gene regulation, cell cycle progression, DNA damage response, chromatin remodeling, ribosomal biogenesis, and RNA splicing. It functions as a reader of histone modifications and interacts with multiple chromatin-modifying complexes and the cell cycle machinery. PELP1 is highly expressed in hormone-responsive tissues and is upregulated in several hormone-driven cancers, contributing to tumor progression, endocrine resistance, and metastasis, making it a promising biomarker and therapeutic target in oncology, particularly for breast cancer. Direct therapeutic targeting remains challenging due to its role as a non-enzymatic transcription coregulator.

Other names

modulator of non-genomic activity of estrogen receptorMNARP160transcription factor HMX3proline, glutamate and leucine rich protein 1proline and glutamic acid rich nuclear protein

Not drug-targeted in the clinic yet; experimental agents potentially inhibit PELP1 expression/function or disrupt its protein-protein interactions, especially affecting estrogen receptor signaling and transcriptional regulation