Somatic mutations in IRE1α regulate keratinocyte migration and survival by differentially activating Rho GTPases.

ABSTRACT: IRE1α is an endoplasmic reticulum (ER) transmembrane protein with cytoplasmic kinase and endoribonuclease (RNase) domains. Under ER stress, IRE1α can splice Xbp1 mRNA enabling translation of this unfolded protein response transcription factor or mediate sequence-specific degradation of mRNAs through regulated IRE1α-dependent decay (RIDD). Somatic mutations in IRE1α occur in many different human cancers including non-melanoma skin cancer (NMSC). To understand their role in skin cancer pathogenesis, we generated immortalized primary mouse keratinocytes with inducible expression of multiple engineered and cancer-associated mutations, including those present in NMSC. All NMSC mutations tested were activating mutations with elevated autophosphorylation and enhanced RIDD activity relative to the

SUBMITTER: Mogre S 

PROVIDER: S-EPMC12517464 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature