KH domain-containing RNA-binding signal transduction-associated protein 1 (KHDRBS1)

KH domain-containing RNA-binding signal transduction-associated protein 1 (KHDRBS1), commonly known as Sam68, is a multifunctional protein that acts as a bridge between signal transduction pathways and RNA metabolism (UniProt Q07666). It belongs to the STAR (Signal Transduction and Activation of RNA) family and contains a KH domain for RNA binding, along with several protein-protein interaction motifs (NCBI Gene 10657). Sam68 regulates critical cellular processes including alternative splicing, RNA transport, and translation, often in response to external stimuli like growth factors or DNA damage (PubMed 31430471). In oncology, Sam68 is frequently overexpressed and promotes the progression of various cancers, such as prostate and breast cancer, by modulating the splicing of genes like CD44 and Bcl-x (PubMed 26153898). It also plays a significant role in viral replication, particularly for HIV-1, where it facilitates the nuclear export of viral RNA (PubMed 11435610). While no drugs targeting Sam68 are currently FDA-approved, it is an active area of research for small molecule inhibitors and antisense oligonucleotides aimed at disrupting its RNA-binding or signaling functions to treat cancer and viral infections. The protein's ability to be post-translationally modified by kinases and methyltransferases allows it to integrate various cellular signals to control gene expression at the post-transcriptional level. Consequently, Sam68 is considered a promising therapeutic target for precision medicine in cancer and infectious diseases.

Other names

Sam68Src-associated in mitosis 68 kDa proteinp68GAP-associated tyrosine phosphoprotein p62RNA-binding protein 1

Inhibition of RNA-binding activity to prevent the splicing of oncogenic isoforms, disruption of protein-protein interactions with signaling kinases, and modulation of viral RNA nuclear export.