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Originally published as MBC in Press, 10.1091/mbc.E07-05-0509 on October 17, 2007

Vol. 18, Issue 12, 5139-5153, December 2007

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Identification of Yeast IQGAP (Iqg1p) as an Anaphase-Promoting-Complex Substrate and Its Role in Actomyosin-Ring-Independent CytokinesisFormula

Nolan Ko*,{dagger}, Ryuichi Nishihama*,{dagger}, Gregory H. Tully{ddagger}, Denis Ostapenko§, Mark J. Solomon§, David O. Morgan{ddagger}, and John R. Pringle*,{dagger}

*Department of Biology, University of North Carolina, Chapel Hill, NC 27599; {dagger}Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305; {ddagger}Department of Physiology, University of California, San Francisco, San Francisco, CA 94143; and §Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520

Submitted May 30, 2007; Revised October 1, 2007; Accepted October 9, 2007
Monitoring Editor: Orna Cohen-Fix

In the yeast Saccharomyces cerevisiae, a ring of myosin II forms in a septin-dependent manner at the budding site in late G1. This ring remains at the bud neck until the onset of cytokinesis, when actin is recruited to it. The actomyosin ring then contracts, septum formation occurs concurrently, and cytokinesis is soon completed. Deletion of MYO1 (the only myosin II gene) is lethal on rich medium in the W303 strain background and causes slow-growth and delayed-cell-separation phenotypes in the S288C strain background. These phenotypes can be suppressed by deletions of genes encoding nonessential components of the anaphase-promoting complex (APC/C). This suppression does not seem to result simply from a delay in mitotic exit, because overexpression of a nondegradable mitotic cyclin does not suppress the same phenotypes. Overexpression of either IQG1 or CYK3 also suppresses the myo1{Delta} phenotypes, and Iqg1p (an IQGAP protein) is increased in abundance and abnormally persistent after cytokinesis in APC/C mutants. In vitro assays showed that Iqg1p is ubiquitinated directly by APC/CCdh1 via a novel recognition sequence. A nondegradable Iqg1p (lacking this recognition sequence) can suppress the myo1{Delta} phenotypes even when expressed at relatively low levels. Together, the data suggest that compromise of APC/C function allows the accumulation of Iqg1p, which then promotes actomyosin-ring-independent cytokinesis at least in part by activation of Cyk3p.


This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-05-0509) on October 17, 2007.

Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: John R. Pringle (jpringle{at}stanford.edu).

Abbreviations used: APC/C, anaphase-promoting complex or cyclosome; DB, destruction box; FACS, fluorescence-activated cell sorter; 5-FOA, 5-fluoroorotic acid.




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