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PIP degron-stabilized Dacapo/p21(Cip)(1) and mutations in ago act in an anti- versus pro-proliferative manner, yet both trigger an increase in Cyclin E levels
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.ORCID-id: 0000-0001-7250-234x
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi, infektion och inflammation. Linköpings universitet, Medicinska fakulteten.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten. Univ Queensland, Australia.ORCID-id: 0000-0001-5095-541X
2019 (engelsk)Inngår i: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 146, nr 13, artikkel-id UNSP dev175927Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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 p21(Cip)(1) and Drosophila Dacapo (Dap) proteins. Both the CycE and Cip/Kip family proteins are under elaborate control via protein degradation, mediated by the Cullin-RING ligase (CRL) family of ubiquitin ligase complexes. The CRL complex SCFFoxw7/Ago targets phosphorylated CycE, whereas p21(Cip)(1) and Dap are targeted by the CRLCdf2 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 and p21(Cip)(1) degradation during Drosophila CNS development. We find that ago mutants display over-proliferation, accompanied by elevated CycE expression levels. By contrast, expression of PIP degron mutant Dap and p21(Cip)(1) 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.

sted, utgiver, år, opplag, sider
COMPANY BIOLOGISTS LTD , 2019. Vol. 146, nr 13, artikkel-id UNSP dev175927
Emneord [en]
CKI; PIP degron; CNS proliferation; Protein degradation
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-159153DOI: 10.1242/dev.175927ISI: 000475477400019PubMedID: 31289041OAI: oai:DiVA.org:liu-159153DiVA, id: diva2:1339652
Merknad

Funding Agencies|Swedish Vetenskapsradet [2017-04061]; Knut och Alice Wallenbergs Stiftelse [KAW2012.0101]; Cancerfonden [CAN2017/257]; Royal Swedish Academy of Sciences

Tilgjengelig fra: 2019-07-30 Laget: 2019-07-30 Sist oppdatert: 2020-03-30

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