Protein phosphatase EYA1 regulates the dephosphorylation and turnover of BCL2L12 to promote glioma development.

ABSTRACT: Glioma is the most prevalent and deadly type of intracranial tumor. Understanding the molecular drivers and their underlying mechanisms in glioma development is urgently needed. EYA1 is a unique protein phosphatase that drives gliomagenesis, yet its substrates remain largely uncharacterized. In this study, we identify BCL2L12 (BCL2-like 12), a critical oncoprotein in glioma, as a novel substrate of EYA1 phosphatase in glioma cells. Our findings demonstrate that EYA1 dephosphorylates BCL2L12 at threonine-33 (T33), which in turn protects BCL2L12 from ubiquitination and subsequent proteasomal degradation. Our results indicate that BCL2L12 partially mediates the oncogenic roles of EYA1 in promoting glioma cell proliferation, highlighting the significance of EYA1's dephosphorylation of BCL2L12

SUBMITTER: Wei T 

PROVIDER: S-EPMC11781168 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature