Ankyrin repeat and SOCS box protein 2 (ASB2)

Ankyrin repeat and SOCS box protein 2 (ASB2) is a member of the ankyrin repeat and SOCS box protein family and acts as the substrate-recognition subunit of a multimeric E3 ubiquitin-protein ligase complex (the Elongin-Cullin-SOCS box [ECS] complex). ASB2 binds target proteins—most notably actin-binding proteins such as filamin A and filamin B—and facilitates their ubiquitination and subsequent proteasomal degradation. Expression of ASB2 is induced by all-trans retinoic acid and Notch signaling, and it plays a pivotal role in hematopoietic cell differentiation, cytoskeleton remodeling, and suppression of cell proliferation, especially in myeloid leukemia cells. In addition, ASB2 can target the Mixed Lineage Leukemia (MLL) protein for degradation, influencing transcriptional programs critical to cell fate. There are multiple alternatively spliced variants of ASB2, with ASB2α and ASB2β being the most studied, which show some substrate specificity. Alteration or dysregulation of ASB2 is linked to leukemia and may be involved in cardiac and muscular development. No clinical drugs directly target ASB2, but it is considered a research target due to its central role in the regulated degradation of disease-relevant proteins.

Other names

Ankyrin repeat and SOCS box containing 2ASB-2ankyrin repeat and SOCS box-containing protein 2aASB2α (isoform), ASB2β (isoform)Ankyrin repeat and SOCS box protein 2

Not applicable (no drugs directly targeting ASB2 currently). Where targeted in research, mechanism would involve inhibition or modulation of its E3 ligase activity to alter proteasomal degradation of key substrates (e.g., filamins, MLL).