2. Academic Validation
  3. APC/C and SCF(cyclin F) Constitute a Reciprocal Feedback Circuit Controlling S-Phase Entry

APC/C and SCF(cyclin F) Constitute a Reciprocal Feedback Circuit Controlling S-Phase Entry

  • Cell Rep. 2016 Sep 20;16(12):3359-3372. doi: 10.1016/j.celrep.2016.08.058.
Rajarshi Choudhury 1,  Thomas Bonacci 1,  Anthony Arceci 1,  Debojyoti Lahiri 2,  Christine A Mills 1,  Jennifer L Kernan 1,  Timothy B Branigan 3,  James A DeCaprio 3,  Daniel J Burke 2,  Michael J Emanuele 4
Affiliations

Affiliations

  • 1 Lineberger Comprehensive Cancer Center and Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 2 Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695, USA.
  • 3 Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • 4 Lineberger Comprehensive Cancer Center and Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: [email protected].
PMID: 27653696 DOI: 10.1016/j.celrep.2016.08.058
Abstract

The anaphase promoting complex/cyclosome (APC/C) is an ubiquitin ligase and core component of the cell-cycle oscillator. During G1 phase, APC/C binds to its substrate receptor Cdh1 and APC/C(Cdh1) plays an important role in restricting S-phase entry and maintaining genome integrity. We describe a reciprocal feedback circuit between APC/C and a second ubiquitin ligase, the SCF (Skp1-Cul1-F box). We show that cyclin F, a cell-cycle-regulated substrate receptor (F-box protein) for the SCF, is targeted for degradation by APC/C. Furthermore, we establish that Cdh1 is itself a substrate of SCF(cyclin F). Cyclin F loss impairs Cdh1 degradation and delays S-phase entry, and this delay is reversed by simultaneous removal of Cdh1. These data indicate that the coordinated, temporal ordering of cyclin F and Cdh1 degradation, organized in a double-negative feedback loop, represents a fundamental aspect of cell-cycle control. This mutual antagonism could be a feature of other oscillating systems.

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