Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2017 Feb 16:6:e25001.
doi: 10.7554/eLife.25001.

Micromanaging checkpoint proteins

Affiliations
Comment

Micromanaging checkpoint proteins

Andrea Ciliberto et al. Elife. .

Abstract

The kinase Mps1, long known to be the 'boss' in mitotic checkpoint signaling, phosphorylates multiple proteins in the checkpoint signaling cascade.

Keywords: E. coli; S. cerevisiae; S. pombe; biochemistry; cell biology; cell cycle; human; kinetochore; protein kinase; spindle checkpoint; xenopus.

PubMed Disclaimer

Conflict of interest statement

The authors declare that no competing interests exist.

Figures

Figure 1.
Figure 1.. The kinase Mps1 and its role in mitotic checkpoint signaling.
(A) Mps1 phosphorylates (P) three different proteins to promote the assembly of the mitotic checkpoint complex. It phosphorylates the kinetochore protein KNL1 to recruit the checkpoint protein complex Bub1-Bub3 to KNL1 (1). It phosphorylates Bub1, which allows this protein to interact with another checkpoint protein, Mad1 (2). It also phosphorylates Mad1, which promotes the binding of Mad2 to the regulatory protein Cdc20 (3). Ji et al. propose that phosphorylated Mad1 binds to Cdc20, thereby positioning the latter for capture by Mad2. (B) The checkpoint (represented by the STOP sign) is only active when Mps1 has phosphorylated all three proteins, KNL1, Bub1, and Mad1. (C) Checkpoint activity (y-axis) plotted as a function of Mps1 kinase activity (x-axis) for the phosphorylation of one (P), two (PP) or all three sites (PPP).

Comment on

References

    1. Aravamudhan P, Goldfarb AA, Joglekar AP. The kinetochore encodes a mechanical switch to disrupt spindle assembly checkpoint signalling. Nature Cell Biology. 2015;17:868–879. doi: 10.1038/ncb3179. - DOI - PMC - PubMed
    1. Faesen AC, Thanasoula M, Maffini S, Breit C, Müller F, van Gerwen S, Bange T, Musacchio A. Basis of catalytic assembly of the mitotic checkpoint complex. Nature. 2017 doi: 10.1038/nature21384. - DOI - PMC - PubMed
    1. Ferrell JE, Ha SH. Ultrasensitivity part II: multisite phosphorylation, stoichiometric inhibitors, and positive feedback. Trends in Biochemical Sciences. 2014;39:556–569. doi: 10.1016/j.tibs.2014.09.003. - DOI - PMC - PubMed
    1. Hardwick KG, Weiss E, Luca FC, Winey M, Murray AW. Activation of the budding yeast spindle assembly checkpoint without mitotic spindle disruption. Science. 1996;273:953–956. doi: 10.1126/science.273.5277.953. - DOI - PubMed
    1. Heinrich S, Sewart K, Windecker H, Langegger M, Schmidt N, Hustedt N, Hauf S. Mad1 contribution to spindle assembly checkpoint signalling goes beyond presenting Mad2 at kinetochores. EMBO Reports. 2014;15:291–298. doi: 10.1002/embr.201338114. - DOI - PMC - PubMed

Substances

LinkOut - more resources