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Molecular and Cellular Biology, June 2008, p. 3652-3662, Vol. 28, No. 11
0270-7306/08/$08.00+0     doi:10.1128/MCB.01923-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Hice1, a Novel Microtubule-Associated Protein Required for Maintenance of Spindle Integrity and Chromosomal Stability in Human Cells{triangledown} ,{dagger}

Guikai Wu,1 Yi-Tzu Lin,1 Randy Wei,1 Yumay Chen,2 Zhiyin Shan,3 and Wen-Hwa Lee1*

Department of Biological Chemistry,1 Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, California 92697,3 Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 782452

Received 24 October 2007/ Returned for modification 26 November 2007/ Accepted 10 March 2008

Spindle integrity is critical for efficient mitotic progression and accurate chromosome segregation. Deregulation of spindles often leads to structural and functional aberrations, ultimately promoting segregation errors and aneuploidy, a hallmark of most human cancers. Here we report the characterization of a previously identified human sarcoma antigen (gene located at 19p13.11), Hice1, an evolutionarily nonconserved 46-kDa coiled-coil protein. Hice1 shows distinct cytoplasmic localization and associates with interphase centrosomes and mitotic spindles, preferentially at the spindle pole vicinity. Depletion of Hice1 by RNA interference resulted in abnormal and unstable spindle configurations, mitotic delay at prometaphase and metaphase, and elevated aneuploidy. Conversely, loss of Hice1 had minimal effects on interphase centrosome duplication. We also found that both full-length Hice1 and Hice1-N1, which is composed of 149 amino acids of the N-terminal region, but not the mutant lacking the N-terminal region, exhibited activities of microtubule bundling and stabilization at a near-physiological concentration. Consistently, overexpression of Hice1 rendered microtubule bundles in cells resistant to nocodazole- or cold-treatment-induced depolymerization. These results demonstrate that Hice1 is a novel microtubule-associated protein important for maintaining spindle integrity and chromosomal stability, in part by virtue of its ability to bind, bundle, and stabilize microtubules.

* Corresponding author. Mailing address: Department of Biological Chemistry, School of Medicine, University of California, Irvine, 124 Sprague Hall, Irvine, CA 92697-4037. Phone: (949) 824-4492. Fax: (949) 824-9767. E-mail: whlee{at}uci.edu

{triangledown} Published ahead of print on 24 March 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, June 2008, p. 3652-3662, Vol. 28, No. 11
0270-7306/08/$08.00+0     doi:10.1128/MCB.01923-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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