Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus

Authors

  • Kasia G. Gora,

    1. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
    2. Howard Hughes Medical Institute, Cambridge, MA, USA
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    • These authors contributed equally.
  • Amber Cantin,

    1. Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA, USA
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    • These authors contributed equally.
  • Matthew Wohlever,

    1. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
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  • Kamal K. Joshi,

    1. Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA, USA
    2. Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA, USA
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  • Barrett S. Perchuk,

    1. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
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  • Peter Chien,

    Corresponding author
    1. Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA, USA
    • Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA, USA
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  • Michael T. Laub

    Corresponding author
    1. Howard Hughes Medical Institute, Cambridge, MA, USA
    • Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
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For correspondence. E-mail laub@mit.edu; Tel. 617 324 0418; Fax 617 253 8699; E-mail pchien@biochem.umass.edu; Tel. 4135452310; Fax 4135453291.

Summary

Cell cycle transitions are often triggered by the proteolysis of key regulatory proteins. In Caulobacter crescentus, the G1-S transition involves the degradation of an essential DNA-binding response regulator, CtrA, by the ClpXP protease. Here, we show that another critical cell cycle regulator, SciP, is also degraded during the G1-S transition, but by the Lon protease. SciP is a small protein that binds directly to CtrA and prevents it from activating target genes during G1. We demonstrate that SciP must be degraded during the G1-S transition so that cells can properly activate CtrA-dependent genes following DNA replication initiation and the reaccumulation of CtrA. These results indicate that like CtrA, SciP levels are tightly regulated during the Caulobacter cell cycle. In addition, we show that formation of a complex between CtrA and SciP at target promoters protects both proteins from their respective proteases. Degradation of either protein thus helps trigger the destruction of the other, facilitating a cooperative disassembly of the complex. Collectively, our results indicate that ClpXP and Lon each degrade an important cell cycle regulator, helping to trigger the onset of S phase and prepare cells for the subsequent programmes of gene expression critical to polar morphogenesis and cell division.

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