PIP degron-stabilized Dacapo/p21Cip1 and mutations in ago act in an anti- versus pro-proliferative manner, yet both trigger an increase in Cyclin E levels

ABSTRACT: During cell cycle progression, the activity of the CycE-Cdk2 complex gates S-phase entry. CycE-Cdk2 is inhibited by CDK inhibitors (CKIs) of the Cip/Kip family, which include the human p21Cip1 and Drosophila Dacapo proteins. Both the CycE and Cip/Kip proteins are under elaborate control via protein degradation, mediated by the Cullin-Ring-Ligase (CRL) family of ubiquitin ligase complexes. The CRL complex SCFFbxw7/Ago targets phosphorylated CycE while p21Cip1 and Dap are targeted by the CRL4Cdt2 complex, binding to the PIP degron. The role of CRL-mediated degradation of CycE and Cip/Kip proteins during CNS development is not well understood. Here, we analyse the role of ago (Fbxw7) mediated CycE degradation and of Dap/p21Cip1 degradation during Drosophila CNS development. We find that ago mutants display over-proliferation, accompanied by elevated CycE expression levels. In contrast, expression of PIP degron mutant Dap/p21Cip1 transgenes inhibit proliferation. However, surprisingly, this is also accompanied by elevated CycE levels. Hence, ago mutation and PIP degron Cip/Kip transgenic expression trigger opposite effects on proliferation, but similar effects on CycE levels.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE133825 | GEO | 2019/07/06

REPOSITORIES: GEO