Cyclin C promotes pancreatic developmentand suppresses cancer initiation by maintenance of the autophagy-lysosome pathway.

Authors

Sara E Hanley, Kathy Q Cai, Stephen D Willis, David C Stieg, Andres J Klein-Szanto, Kerry S Campbell, Randy Strich

Published in

iScience. Volume 29. Issue 3. Pages 114949. Mar 20, 2026. Epub Feb 07, 2026.

Abstract

Cyclin C (CCNC) is a component of the mediator complex that regulates gene transcription. In stressed cells, cyclin C also translocates to the mitochondria to induce fission and stimulate programmed cell death. The present study found that cyclin C is required for autophagy lysosome pathway gene transcription in mouse embryonic fibroblasts. In vivo, pancreatic ablation of Ccnc caused islet atrophy and acinar cell damage. However, Ccnc pancreatic ablation caused more dramatic phenotypes than autophagy mutants alone, including increased mortality and accelerated precancerous lesion formation. Previous studies found that autophagy-deficient pancreatic cells expressing oncogenic Kras undergo Tp53-dependent cell death. However, Kras ^G12D ;Ccnc ^-/- pancreata did not undergo cell death, suggesting a role for the mitochondrial cyclin C function. Finally, loss of CCNC activity rendered cells hypersensitive to proteasome inhibitors. These findings identify multiple roles for cyclin C in promoting pancreatic health and suggest a new strategy to target pancreatic neoplasms by inhibiting proteasome function.

PMID:
41867622
Bibliographic data and abstract were imported from PubMed on 15 Sep 2026.

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