Reciprocal interactions among Cobll1, PACSIN2, and SH3BP1 regulate drug resistance in chronic myeloid leukemia

Abstract

Cobll1 affects blast crisis (BC) progression and tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia (CML). PACSIN2, a novel Cobll1 binding protein, activates TKI-induced apoptosis in K562 cells, and this activation is suppressed by Cobll1 through the interaction between PACSIN2 and Cobll1.PACSIN2 also binds and inhibits SH3BP1 which activates the downstream Rac1 pathway and induces TKI resistance. PACSIN2 competitively interacts with Cobll1 or SH3BP1 with a higher affinity for Cobll1. Cobll1 preferentially binds to PACSIN2, releasing SH3BP1 to promote the SH3BP1/Rac1 pathway and suppress

PACSIN2as a modulator of autophagy and mercaptopurine cytotoxicity: mechanisms in lymphoid and intestinal cells

“…Different autophagy modulators interact with LC3 ( Mizushima et al, 2010 ; Birgisdottir et al, 2013 ; Chun & Kim, 2018 ). PACSIN2 protein shows different interacting region domains, responsible for a physical interaction with other proteins, such as Rac-1, Cobll1, and SH3BP1, that modulate different cellular biological processes and impacts on tyrosine kinase inhibitor sensitivity in in vitro models ( de Kreuk et al, 2011 ; Park et al, 2022 ). Interestingly, we found that PACSIN2 presents a LIR domain in its N-terminal amino acid sequence, responsible for a physical interaction with LC3 that may permit to exert PACSIN2 regulation on autophagy.…”