RNA-binding protein 5 (RBM5) (RBM5)

RNA-binding protein 5 (RBM5), also known as LUCA-15 or H37, is a multi-functional protein encoded by the RBM5 gene located on the 3p21.3 chromosomal region, a site frequently deleted in various cancers (PubMed: 16585163). It primarily functions as a component of the spliceosome A complex, where it regulates the alternative splicing of pre-mRNAs, particularly those involved in apoptosis and cell cycle control, such as Fas, Caspase-2, and NUMB (PubMed: 16169070, 21256132). In many solid tumors, including lung and breast cancer, RBM5 acts as a tumor suppressor, and its downregulation is associated with tumor progression and resistance to chemotherapy agents like cisplatin (PubMed: 16546166). Conversely, recent research has identified RBM5 as a critical dependency in acute myeloid leukemia (AML), where it regulates the transcription of the oncogenic factor HOXA9, making it a potential therapeutic target for inhibition in this context (PubMed: 38216972). Therapeutic strategies under investigation include the use of small molecules like indisulam to induce its degradation and the development of RBM5-targeted therapies to resensitize cancer cells to existing treatments.

Other names

LUCA-15H37G15RNA-binding motif protein 5Renal carcinoma antigen NY-REN-93p21.3 tumor suppressor gene

Molecular glue-mediated degradation (via DCAF15), Induction of gene expression, Sensitization to DNA-damaging agents