PC4 and SFRS1-interacting protein (PSIP1) (PSIP1)

PC4 and SFRS1-interacting protein (PSIP1), widely known as Lens epithelium-derived growth factor (LEDGF/p75), is a chromatin-associated protein that functions as a transcriptional coactivator and a critical host factor for HIV-1 infection [UniProt O75475]. The PSIP1 mRNA encodes a protein that tethers the HIV-1 pre-integration complex to the host cell's chromatin, specifically directing viral integration into transcriptionally active regions of the genome [PubMed: 21115976]. Beyond its role in viral pathogenesis, PSIP1 is involved in cellular stress responses, DNA damage repair, and the regulation of cell survival pathways [PubMed: 23835560]. In oncology, PSIP1 is frequently overexpressed and has been implicated in the progression of various malignancies, including leukemia and prostate cancer, where it promotes resistance to apoptosis [PubMed: 26334377]. Therapeutic targeting of PSIP1 primarily focuses on disrupting its interaction with HIV-1 integrase using small molecules called LEDGINs or utilizing RNA interference (RNAi) to knockdown PSIP1 mRNA levels [PubMed: 22423967]. However, because PSIP1 is essential for maintaining normal cellular homeostasis and genomic stability, therapeutic strategies must carefully manage the risk of off-target effects on host transcription and DNA repair [PubMed: 25108353].

Other names

Lens epithelium-derived growth factorLEDGFp75Dense fine speckled 70 kDa antigenDFS70Transcriptional coactivator p75

RNA interference-mediated degradation of mRNA; Allosteric inhibition of HIV-1 integrase binding to the LEDGF/p75 protein product