SH3 domain-containing ring finger protein 3 (SH3RF3)

SH3 domain-containing ring finger protein 3 (SH3RF3, also known as POSH2) is an "E3 ubiquitin-protein ligase" and scaffold protein characterized by an N-terminal RING finger domain and multiple SH3 domains[1][2][3][4][10]. SH3RF3 facilitates the transfer of ubiquitin to target proteins—regulating their degradation—and forms protein complexes that organize and modulate signaling cascades, most notably the JNK (c-Jun N-terminal kinase) pathway[1][3][5]. It plays a prominent role in the regulation of cancer stem-like cells by promoting JNK-JUN-mediated transcription of the pentraxin family protein PTX3, thereby expanding the cancer stem cell subpopulation in breast cancer[1][3]. SH3RF3 has additional implications in other diseases, including acute lymphoblastic leukemia, neurocognitive disorders, and possibly familial Alzheimer’s disease[1]. Disrupting SH3RF3 function is proposed as a rational therapeutic strategy in cancers characterized by aggressive stem-like traits, but no clinically approved drugs or inhibitor compounds are currently described in the literature[3][10].

Other names

POSH2SH3MD4FLJ00204SH3 multiple domains protein 4plenty of SH3s-2E3 ubiquitin-protein ligase SH3RF3SH3 domain containing ring finger 3

Not applicable; no direct drugs or inhibitors reported in the literature. Theoretically, potential mechanisms would include inhibition of E3 ligase/scaffold activity to disrupt JNK-JUN pathway signaling in cancer stem cells.