PSIP1

Description

The PSIP1 (PC4 and SRSF1 interacting protein 1) is a protein-coding gene located on chromosome 9.

PSIP1, also known as Lens epithelium-derived growth factor (LEDGF/p75), Dense fine speckles 70kD protein (DFS 70) or transcriptional coactivator p75/p52, is a protein that in humans is encoded by the PSIP1 gene. PSIP1 has not been clearly linked to a specific cellular mechanism. The term LEDGF/p75 has entered common usage based on the initial characterization of PSIP1, however this is a misnomer, as the protein is present in most tissues and has no direct role in the development of lens epithelium. LEDGF/p75, a transcription coactivator, gained prominence as a host factor that assists HIV integration and is probably the only integrase interactor whose knock-down severely affects the HIV integration levels. The interaction between HIV integrase and human LEDGF/p75 is a promising target for anti-HIV drug discovery. LEDGF/p75 recruits MLL complexes to HOX genes to regulate their expression. LEDGF/p52 is shown to recruit splicing factors to H3K36 trimethylated chromatin to modulate alternative splicing, also regulates HOTTIP lncRNA, which is shown to regulate HOX genes in cis. LEDGF/p75 is a 60kDa, 530-amino-acid-long protein. The N-terminal portion of the protein consists of a PWWP domain, a nuclear localization sequence, and two copies of the AT-hook DNA binding motif. The C-terminal portion of LEDGF/p75 contains a structure termed the integrase-binding domain, which interacts with lentiviral integrase proteins as well as numerous cellular proteins.

PSIP1, also known as LEDGF/p75, is a transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. It plays a key role in lens epithelial cell gene regulation and stress responses, potentially contributing to lens epithelial to fiber cell terminal differentiation and protecting against stress-induced apoptosis. Isoform 2 acts as a more general and stronger transcriptional coactivator, and may also coordinate pre-mRNA splicing. PSIP1 is a cellular cofactor for lentiviral integration.

PSIP1 is also known as DFS70, LEDGF, PAIP, PSIP2, p52, p75.

Associated Diseases

WES Whole Exome Sequencing