UC San Diego

RASSF2 belongs to the Ras-association domain family (RASSFs) and was previously identified as a transcriptional target of RUNX1-ETO associated with the t(8;21) acute myeloid leukemia. RASSF2 was reported to interact with Hippo kinase MST1/MST2 and RAS family GTPase KRAS but its association with other GTPases remained unexplored. In this study, we carefully selected 19 small GTPases guided by their specific expression in bone marrow and association with proteins proximal to RASSF2. As a result, we discovered six novel small GTPases that interact with RASSF2, namely Rab32, Rac2, RIT1, RhoH, Rab8a, and RhoA. Structural modeling predictions suggest the possibility of direct bindings between these small GTPases and RASSF2. Notably, the expression levels of Rac2 and Rab32 correlate with the survival of AML patients. This study advances our understanding of RASSF2's biological role as a Ras effector-like protein and provides valuable insights into RASSF2’s potential contributions to hematopoiesis and the development of AML.