Abstract 6797: Mechanisms of nuclear MCL1 mediated chemoresistance

Abstract The upregulation of anti-apoptotic BCL2 family members is a major mechanism of chemoresistance in many solid cancers. MCL1 (myeloid cell leukemia 1), an anti-apoptotic member of BCL2 family, is overexpressed in many solid tumors and associates with poor prognosis and therapeutic failure. In addition to its anti-apoptotic functions, MCL1 reportedly has non-apoptotic, nuclear functions that play a role in DNA damage response, cell cycle, and chemoresistance. However, the nuclear functions of MCL1 remain sparse and unelucidated. Our lab has investigated the nuclear interactome of MCL1 in solid cancer cells by implementing a proximity biotinylation approach. As a result, we have identified many novel MCL1 interactors in the nucleus, adding to MCL1’s repertoire of interactors. We are currently investigating whether our newly defined nuclear interactors of MCL1 play a role in MCL1-mediated chemoresistance. Overall, we are hoping to further elucidate the role of MCL1 in the nucleus in mediating chemoresistance. Citation Format: Kylin A. Emhoff, Jesse A. Coker, Jan J. Melenhorst. Mechanisms of nuclear MCL1 mediated chemoresistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6797.