A novel human protein of the maternal centriole is required for the final stages of cytokinesis and entry into S phase.
Centrosomes nucleate microtubules and contribute to mitotic spindle organization and function. They also participate in cytokinesis and cell cycle progression in ways that are poorly understood. Here we describe a novel human protein called centriolin that localizes to the maternal centriole and functions in both cytokinesis and cell cycle progression. Centriolin silencing induces cytokinesis failure by a novel mechanism whereby cells remain interconnected by long intercellular bridges. Most cells continue to cycle, reenter mitosis, and form multicellular syncytia. Some ultimately divide or undergo apoptosis specifically during the protracted period of cytokinesis. At later times, viable cells arrest in G1/G0. The cytokinesis activity is localized to a centriolin domain that shares homology with Nud1p and Cdc11p, budding and fission yeast proteins that anchor regulatory pathways involved in progression through the late stages of mitosis. The Nud1p-like domain of centriolin binds Bub2p, another component of the budding yeast pathway. We conclude that centriolin is required for a late stage of vertebrate cytokinesis, perhaps the final cell cleavage event, and plays a role in progression into S phase.
University of Massachusetts Medical School, Department of Molecular Medicine, Worcester, MA 01605, USA.
Adam
A
Gromley
Agata
A
Jurczyk
James
J
Sillibourne
Ensar
E
Halilovic
Mette
M
Mogensen
Irina
I
Groisman
Maureen
M
Blomberg
Stephen
S
Doxsey
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001483:Base Sequence / Q000235:genetics; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D002455:Cell Division / Q000235:genetics*; D002502:Centrioles / Q000378:metabolism* / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis; D003851:Deoxyribonucleases / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D005057:Eukaryotic Cells / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D034741:RNA, Small Interfering; D016196:S Phase / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012359:tRNA Methyltransferases
D000906:Antibodies; C070351:BUB2 protein, S cerevisiae; C099502:CDC11 protein, S cerevisiae; C474898:CNTRL protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D034741:RNA, Small Interfering; D029701:Saccharomyces cerevisiae Proteins; D012359:tRNA Methyltransferases; D003851:Deoxyribonucleases; C077501:TRM2 protein, S cerevisiae