This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dallol, A. Articles by Latif, F. Search for Related Content PubMed PubMed Citation Articles by Dallol, A. Articles by Latif, F.

Depletion of the Ras Association Domain Family 1, Isoform A–Associated Novel Microtubule-Associated Protein, C19ORF5/MAP1S, Causes Mitotic Abnormalities

¹ Section of Medical and Molecular Genetics, Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham, United Kingdom and ² Molecular Pathology Laboratory, Department of Pathology, Kuwait University, Faculty of Medicine, Safat, Kuwait

Requests for reprints: Farida Latif, Section of Medical and Molecular Genetics, Division of Reproductive and Child Health, The Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom. Phone: 44-121-627-2741; Fax: 44-121-627-2618; E-mail: f.latif{at}bham.ac.uk or Ashraf Dallol, E-mail: a.dallol{at}bham.ac.uk.

Ras association domain family 1, isoform A (RASSF1A) is a novel tumor suppressor gene that is found to be inactivated in more than 40 types of sporadic cancers. In addition, mouse Rassf1a knockout models have an increased frequency of spontaneous and induced tumors. The mechanisms by which RASSF1A exerts its tumor suppression activities or the pathways it can regulate are not yet fully understood. Using yeast two-hybrid system, we have previously identified C19ORF5/MAP1S as the major RASSF1A-interacting protein. C19ORF5 has two conserved microtubule-associated regions and may function to anchor RASSF1A to the centrosomes. In this study, we have analyzed the cellular functions of C19ORF5. By using small interfering RNA–mediated depletion and time-lapse video microscopy, we show that C19ORF5 knockdown causes mitotic abnormalities that consist of failure to form a stable metaphase plate, premature sister chromatid separation, lagging chromosomes, and multipolar spindles. We also show that a fraction of C19ORF5 localizes to the spindle microtubules. Additionally, we show here that C19ORF5 localizes to the microtubule-organizing centers during microtubule regrowth after nocodazole washout. Knockdown of C19ORF5 disrupts the microtubule-organizing center and results in microtubule nucleation from several sites. Whereas the localization of pericentrin is not affected, - and -tubulin localization and sites of nucleation are greatly altered by C19ORF5 depletion. This may indicate that C19ORF5 plays a role in anchoring the microtubule-organizing center to the centrosomes. In addition, we show that the NH₂ terminus of C19ORF5 is essential for this process. This novel role for C19ORF5 could explain the resulting mitotic abnormalities that occur on its depletion and can potentially provide an underlying mechanism for the frequent centrosome and microtubule abnormalities detected in several cancers. [Cancer Res 2007;67(2):492–500]

This article has been cited by other articles:

				J. Tegha-Dunghu, B. Neumann, S. Reber, R. Krause, H. Erfle, T. Walter, M. Held, P. Rogers, K. Hupfeld, T. Ruppert, et al. EML3 is a nuclear microtubule-binding protein required for the correct alignment of chromosomes in metaphase J. Cell Sci., May 15, 2008; 121(10): 1718 - 1726. [Abstract] [Full Text] [PDF]

				I. Peters, B. Vaske, K. Albrecht, M. A. Kuczyk, U. Jonas, and J. Serth Adiposity and Age are Statistically Related to Enhanced RASSF1A Tumor Suppressor Gene Promoter Methylation in Normal Autopsy Kidney Tissue Cancer Epidemiol. Biomarkers Prev., December 1, 2007; 16(12): 2526 - 2532. [Abstract] [Full Text] [PDF]

				H. Donninger, M. D. Vos, and G. J. Clark The RASSF1A tumor suppressor J. Cell Sci., September 15, 2007; 120(18): 3163 - 3172. [Abstract] [Full Text] [PDF]