DEPTOR suppresses lymphomagenesis by promoting EGFR degradation via HUWE1 E3 ligase.

ABSTRACT: DEPTOR, a naturally occurring inhibitor of mTOR, plays crucial roles in tumorigenesis and is frequently dysregulated in a variety of human cancers. Interestingly, DEPTOR could act either as a tumor suppressor or as an oncogene in a manner dependent of cellular context or tissue environment. Whether and how DEPTOR regulates lymphomagenesis remains elusive. In this study, we report that in a mouse lymphoma model induced by heterozygous Pten loss, Deptor knockout (KO) markedly accelerates lymphomagenesis, whereas degradation-resistant Deptor^S275A knock-in (KI) variant significantly inhibits it. Furthermore, Deptor KO mice spontaneously developed lymphomas in the later stages of their lifespan, and Deptor KO further shortened overall lifespan in Pten^fl/fl;MMTV-Cre mice. C

SUBMITTER: Xiong X 

PROVIDER: S-EPMC12501038 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature