Speckled 140 kDa protein (SP140) (SP140)

Speckled 140 kDa protein (SP140) is a lymphoid-restricted member of the SP100/SP140 family of nuclear body proteins, primarily expressed in immune cells such as B cells and macrophages [UniProt: P0C0S5]. It functions as an epigenetic reader, utilizing its bromodomain and PHD finger to recognize specific histone modifications, thereby regulating the transcription of genes involved in the innate and adaptive immune response [PubMed: 35051355]. Genetic variations in the SP140 locus are strongly associated with autoimmune and inflammatory conditions, most notably Crohn's disease and primary biliary cholangitis [PubMed: 23128233]. In oncology, SP140 is often downregulated or mutated in chronic lymphocytic leukemia (CLL) and multiple myeloma, suggesting a role in tumor suppression or disease progression [PubMed: 25605872]. Therapeutic interest in SP140 centers on its bromodomain, which can be targeted by small-molecule inhibitors like GSK761 to modulate inflammatory gene expression in diseases like inflammatory bowel disease [PubMed: 35051355]. These inhibitors aim to provide a more selective approach to immune modulation compared to pan-BET inhibitors, potentially reducing systemic toxicity [PubMed: 35051355].

Other names

Nuclear body protein SP140LYSP100Lymphoid-restricted SP100-like proteinSpeckled 140 kDa

Inhibition of the SP140 bromodomain to prevent binding to acetylated histones and modulate inflammatory gene expression