Pelp1, short for Proline-, Glutamic acid- and Leucine-rich protein 1, is a scaffolding protein and a coregulator of several transcription factors and nuclear receptors [2]. It plays essential roles in multiple pathways, such as hormonal signaling, cell cycle progression, ribosomal biogenesis, and the DNA damage response [2]. Its functions are regulated by phosphorylation as it serves as a substrate for numerous kinases [2].

Pelp1 forebrain-specific knockout mice have demonstrated its critical role in mediating both extranuclear and nuclear estrogen receptor (ER) signaling in the brain [1]. This includes its involvement in 17β-estradiol (E2)-induced neuroprotection, anti-inflammatory effects, and regulation of cognitive function [1]. In cancer, knockdown of Pelp1 in hepatocellular carcinoma (HCC) cells reduced cell viability, clonogenicity, and invasion, and high expression of Pelp1 was associated with unfavorable survival outcomes in HCC patients [3]. In glioblastoma, Pelp1 knockdown led to decreased cell viability, survival, migration, and invasion, as it enhances Wnt/β-catenin signaling in this cancer type [4].

In summary, Pelp1 is a crucial regulator in both normal physiological processes, especially in the brain related to estrogen-mediated functions, and in disease conditions such as various cancers. The use of gene knockout models, like the forebrain-specific Pelp1 knockout mice, has been instrumental in revealing its role in these biological processes and disease areas, providing potential therapeutic targets for hormonal cancers and glioblastoma [1,3,4].

References:

1. Thakkar, R, Sareddy, G R, Zhang, Q, Vadlamudi, R K, Brann, D. . PELP1: a key mediator of oestrogen signalling and actions in the brain. In Journal of neuroendocrinology, 30, . doi:10.1111/jne.12484. https://pubmed.ncbi.nlm.nih.gov/28485080/

2. Sareddy, Gangadhara Reddy, Vadlamudi, Ratna K. 2016. PELP1: Structure, biological function and clinical significance. In Gene, 585, 128-134. doi:10.1016/j.gene.2016.03.017. https://pubmed.ncbi.nlm.nih.gov/26997260/

3. Nassar, Khaled Mohamed, Yang, Xue, Baker, Adriana, Vadlamudi, Ratna K, Pratap, Uday P. . PELP1 Is a Novel Therapeutic Target in Hepatocellular Carcinoma. In Cancer research communications, 4, 2610-2620. doi:10.1158/2767-9764.CRC-24-0173. https://pubmed.ncbi.nlm.nih.gov/39258975/

4. Sareddy, Gangadhara R, Pratap, Uday P, Viswanadhapalli, Suryavathi, Brann, Darrell W, Vadlamudi, Ratna K. 2019. PELP1 promotes glioblastoma progression by enhancing Wnt/β-catenin signaling. In Neuro-oncology advances, 1, vdz042. doi:10.1093/noajnl/vdz042. https://pubmed.ncbi.nlm.nih.gov/32309805/