Characterization of Su48, a centrosome protein essential for cell division.
The centrosome functions as the major microtubule-organizing center and plays a vital role in guiding chromosome segregation during mitosis. Centrosome abnormalities are frequently seen in a variety of cancers, suggesting that dysfunction of this organelle may contribute to malignant transformation. In our efforts to identify the protein components of the centrosome and to understand the structure features involved in the assembly and functions of this organelle, we cloned and characterized a centrosome-associated protein called Su48. We found that a coiled coil-containing subdomain of Su48 was both sufficient and required for its centrosome localization. In addition, this structure also modulates Su48 dimerization. Moreover, ectopic expression of Su48 causes abnormal mitosis, and a mutant form of Su48 disrupts the localization of gamma-tubulin to the centrosome. Finally, by microinjection of an anti-Su48 antibody, we found that disruption of normal Su48 functions leads to mitotic failure, possibly due to centrosome defects or incomplete cytokinesis. Thus, Su48 represents a previously unrecognized centrosome protein that is essential for cell division. We speculate that Su48 abnormalities may cause aberrant chromosome segregation and may contribute to aneuploidy and malignant transformation.
Wang
Qiang
Q
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. wangq252@mail.med.upenn.edu
Du
Xiulian
X
Meinkoth
Judy
J
Hirohashi
Yoshihiko
Y
Zhang
Hongtao
H
Liu
Qingdu
Q
Richter
Mark
M
Greene
Mark I
MI
D000818:Animals; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism*; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005260:Female; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008938:Mitosis; D016296:Mutagenesis; D011247:Pregnancy; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques
D003598:Cytoskeletal Proteins; D011993:Recombinant Fusion Proteins