PELP1: Structure, biological function and clinical significance

Abstract

Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein that functions as a coregulator of several transcription factors and nuclear receptors. Notably, the PELP1 protein has a histone-binding domain, recognizes histone modifications and interacts with several chromatin-modifying complexes. PELP1 serves as a substrate of multitude of kinases, and phosphorylation regulates its functions in various complexes. Further, PELP1 plays essential roles in several pathways including hormonal signaling, cell cycle progression, ribosomal biogenesis, and the DNA damage response. PELP1 expression is upregulated in several cancers, its deregulation contributes to therapy resistance, and it is a prognostic biomarker for breast cancer survival. Recent evidence suggests that PELP1 represents a novel therapeutic target for many hormonal cancers. In this review, we summarized the emerging biological properties and functions of PELP1.

PELP1 signaling contributes to medulloblastoma progression by regulating the NF‐κB pathway

“…PELP1 functions are vital in oncogenic processes, such as cell cycle, survival, metastasis, hormone therapy resistance, and autophagy . Several reports have shown that PELP1 downregulation significantly reduced the proliferation, survival, migration, and invasion of cancer cells in multiple cancer types .…”

“…Proline‐, glutamic acid‐, and leucine‐rich protein 1 (PELP1) is a scaffolding protein that regulates several signaling pathways and many biological processes . Structurally, PELP1 has 10 nuclear receptors (NRs) interacting boxes LXXLL motifs that facilitate its interaction with NRs, proline‐rich motifs that facilitate interactions with SRC homology 3 domain‐containing proteins, and C‐terminus glutamic acid‐containing region which assists in interactions with histone proteins .…”

“…Proline‐, glutamic acid‐, and leucine‐rich protein 1 (PELP1) is a scaffolding protein that regulates several signaling pathways and many biological processes . Structurally, PELP1 has 10 nuclear receptors (NRs) interacting boxes LXXLL motifs that facilitate its interaction with NRs, proline‐rich motifs that facilitate interactions with SRC homology 3 domain‐containing proteins, and C‐terminus glutamic acid‐containing region which assists in interactions with histone proteins . PELP1 regulates gene expression by functioning as a coregulator of many transcriptional factors and NRs including estrogen receptor (ER), androgen receptor, progesterone receptor, glucocorticoid receptor, and signal transducer and activator of transcription 3 .…”

“…PELP1 regulates gene expression by functioning as a coregulator of many transcriptional factors and NRs including estrogen receptor (ER), androgen receptor, progesterone receptor, glucocorticoid receptor, and signal transducer and activator of transcription 3 . PELP1 is shown to play a key role in several biological functions such as transcriptional regulation by NRs, chromatin remodeling,cell cycle, DNA damage response, ribosome biogenesis, and RNA splicing …”

NLRP3 Inflammasome Activation in the Brain after Global Cerebral Ischemia and Regulation by 17β‐Estradiol

“…PELP1 is expressed in a variety of tissues, with highest expression in the brain, ovaries, testes, and uterus [16–20]. In addition, PELP1 exhibits both nuclear and cytoplasmic localization [20], and phosphorylation of PELP1 can control its localization, interaction with other proteins, and stability in cells [16, 17]. To understand its importance in E2 actions in the brain, our group recently created a PELP1 forebrain-specific knockout (PELP1 FBKO) mouse model [16].…”