Coordination between the eIF2 kinase GCN2 and p53 signaling supports purine metabolism and the progression of prostate cancer.

ABSTRACT: Cancers invoke various pathways to mitigate external and internal stresses to continue their growth and progression. We previously reported that the eIF2 kinase GCN2 and the integrated stress response are constitutively active in prostate cancer (PCa) and are required to maintain amino acid homeostasis needed to fuel tumor growth. However, although loss of GCN2 function reduces intracellular amino acid availability and PCa growth, there is no appreciable cell death. Here, we discovered that the loss of GCN2 in PCa induces prosenescent p53 signaling. This p53 activation occurred through GCN2 inhibition-dependent reductions in purine nucleotides that impaired ribosome biogenesis and, consequently, induced the impaired ribosome biogenesis checkpoint. p53 signaling induced cell cycle arrest an

SUBMITTER: Cordova RA 

PROVIDER: S-EPMC11826925 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature