PC4 and SFRS1-interacting protein (PSIP1)

PC4 and SFRS1-interacting protein, widely known as LEDGF/p75, is a multifunctional transcriptional coactivator that plays a pivotal role in tethering protein complexes to specific chromatin sites. It is a critical host factor for HIV-1 infection, where it guides the viral pre-integration complex to actively transcribed regions of the host genome by binding to the viral integrase (UniProt: P52298). In the context of oncology, PSIP1 is essential for the development of MLL-rearranged leukemias, acting as a scaffold that stabilizes the interaction between MLL fusion proteins and chromatin (PubMed: 20300081). Beyond its role as a tether, it participates in the cellular stress response, mRNA splicing, and the maintenance of genomic integrity by facilitating the resolution of R-loops and recruiting DNA repair factors like CtIP (PubMed: 25043379). Therapeutic efforts have led to the development of LEDGINs, a class of allosteric inhibitors that block the interaction between LEDGF/p75 and HIV-1 integrase, showing potential for both antiviral therapy and cancer treatment (PubMed: 21102410). However, because PSIP1 is involved in fundamental cellular processes such as DNA repair and developmental gene regulation, systemic inhibition may pose risks of genomic instability or developmental toxicity (PubMed: 22327296). It is also a target of autoantibodies in certain autoimmune conditions, where anti-DFS70 antibodies serve as a diagnostic marker to help rule out systemic autoimmune rheumatic diseases (PubMed: 21273274).

Other names

Lens epithelium-derived growth factorLEDGFp75p52DFS70Transcriptional coactivator p75CLL-associated antigen KW-7

Inhibition of the protein-protein interaction between the LEDGF/p75 integrase-binding domain (IBD) and its binding partners, such as HIV-1 integrase or MLL fusion proteins, to prevent viral integration or oncogenic transcription.