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Hunt Special Lecture

Please cite this article as follows: Hunt T. Getting in and out of mitosis (abstract for video). Special Lecture Wilsede Meeting 2008. Cell Ther Transplant. 2008;1:e.000014.01. doi:10.3205/ctt-2008-en-000014.01

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Getting in and out of mitosis (Video)

Special Lecture Wilsede Meeting 2008

Tim Hunt

Cell Cycle Control Laboratory, Cancer Research UK, South Mimms, UK

Abstract

Cells enter mitosis (more generally, M-phase, and much of our work has been in frog oocytes and eggsand extracts thereof) when CDK1/cyclin complexes are activated. Phosphorylation by these, and othermitotic protein kinases, is responsible for reorganizing the cell and initiating progression to metaphase.

We would like to know how many proteins needs to be phosphorylated how much to bring about thisstate of affairs, and have been trying to enumerate the mitotic targets for various cyclin-CDKcombinations for some time. I’ll talk about our approaches, difficulties and findings.

Exit from mitosis, starting at the metaphase to anaphase transition, occurs when the anaphasepromotingfactor (APC/C) is activated and tags a small number of target proteins, including cyclinsand securin, with polyubiquitin chains that signal their proteolysis by the proteasome. Chromatids partand move to opposite poles of the cell where they decondense and re-form a functional nucleus.

Cytokinesis separates the two daughter cells. Mitotic phosphoproteins revert to their interphase un- orhypo-phosphorylated state.

We recently made the accidental discovery that the activity responsible for this postmitoticdephosphorylation is almost completely inactive in M-phase cell extracts, and is reactivated when cellsexit mitosis. This explains how proteins can become almost completely converted tohyperphosphorylated states: not only are kinases activated, but the counteracting phosphatase(s) areconcomitantly shut down. I will present the evidence that has led us to this conclusion. It stems fromstudies of frog egg extracts released from cytostatic factor (CSF) arrest by added CaCl2, and thediscovery that calcineurin (protein phosphatase 2B) plays a role in escaping the clutches of CSF. But the real work of restoring proteins to their interphase state of hypophosphorylation is performed by anactivity we call ‘Phosphatase X’, whose identity and regulation I shall discuss.

Keywords: mitosis, oocytes, cytokynesis, phosphorylation, phosphatase

Please cite this article as follows: Hunt T. Getting in and out of mitosis (abstract for video). Special Lecture Wilsede Meeting 2008. Cell Ther Transplant. 2008;1:e.000014.01. doi:10.3205/ctt-2008-en-000014.01


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