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Proc Natl Acad Sci U S A
2010 Feb 16;1077:2932-7. doi: 10.1073/pnas.0914874107.
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Discovery of a distinct domain in cyclin A sufficient for centrosomal localization independently of Cdk binding.
Pascreau G
,
Eckerdt F
,
Churchill ME
,
Maller JL
.
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Centrosomes have recently emerged as key regulators of the cell cycle. The G1/S transition requires a functional centrosome, and centrosomal localization of numerous proteins, including cyclin/Cdk complexes, is important for the G2/M transition. Here we identify a modular centrosomal localization signal (CLS) localizing cyclin A to centrosomes independently of Cdk binding. The cyclin A CLS is located in a distinct part of the molecule compared with the cyclin E CLS and includes the MRAIL hydrophobic patch involved in substrate recognition. The cyclin A CLS interacts with p27(KIP1), and expression of p27(KIP1) removes cyclin A but not cyclin E from centrosomes. Expression of the cyclin A CLS displaces both endogenous cyclin A and E from centrosomes and inhibits DNA replication, supporting an emerging concept that DNA replication is linked to centrosomal events. Structural analysis indicates that differences in surface charge and length of the C-terminal helix explain why the MRAIL region in cyclin E is not a functional CLS. These results indicate that the cyclin A CLS may contribute to targeting and recognition of centrosomal Cdk substrates and is required for specific effects of p27(KIP1) on cyclin A-Cdk2.
Bailly,
Cytoplasmic accumulation of cyclin B1 in human cells: association with a detergent-resistant compartment and with the centrosome.
1992, Pubmed
Bailly,
Cytoplasmic accumulation of cyclin B1 in human cells: association with a detergent-resistant compartment and with the centrosome.
1992,
Pubmed
Bentley,
Distinct sequence elements of cyclin B1 promote localization to chromatin, centrosomes, and kinetochores during mitosis.
2007,
Pubmed
Brown,
The crystal structure of cyclin A.
1995,
Pubmed
Cheng,
The role of the phospho-CDK2/cyclin A recruitment site in substrate recognition.
2006,
Pubmed
Cuschieri,
Control at the cell center: the role of spindle poles in cytoskeletal organization and cell cycle regulation.
2007,
Pubmed
De Boer,
Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events.
2008,
Pubmed
Doxsey,
Centrosomes in cellular regulation.
2005,
Pubmed
Doxsey,
Centrosome control of the cell cycle.
2005,
Pubmed
Dulić,
Association of human cyclin E with a periodic G1-S phase protein kinase.
1992,
Pubmed
Ferguson,
Cyclin E-dependent localization of MCM5 regulates centrosome duplication.
2008,
Pubmed
,
Xenbase
Fukasawa,
Oncogenes and tumour suppressors take on centrosomes.
2007,
Pubmed
Gardner,
Hypoxia inhibits G1/S transition through regulation of p27 expression.
2001,
Pubmed
Gillingham,
The PACT domain, a conserved centrosomal targeting motif in the coiled-coil proteins AKAP450 and pericentrin.
2000,
Pubmed
Harper,
Synchronization of cell populations in G1/S and G2/M phases of the cell cycle.
2005,
Pubmed
Hemerly,
Orc1 controls centriole and centrosome copy number in human cells.
2009,
Pubmed
Hinchcliffe,
Requirement of a centrosomal activity for cell cycle progression through G1 into S phase.
2001,
Pubmed
Honda,
The structure of cyclin E1/CDK2: implications for CDK2 activation and CDK2-independent roles.
2005,
Pubmed
Huang,
The disappearance of cyclin B at the end of mitosis is regulated spatially in Drosophila cells.
1999,
Pubmed
Jackman,
Active cyclin B1-Cdk1 first appears on centrosomes in prophase.
2003,
Pubmed
Jackson,
Early events in DNA replication require cyclin E and are blocked by p21CIP1.
1995,
Pubmed
,
Xenbase
Jeffrey,
Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
1995,
Pubmed
Khodjakov,
Centrosomes enhance the fidelity of cytokinesis in vertebrates and are required for cell cycle progression.
2001,
Pubmed
Koff,
Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle.
1992,
Pubmed
Krämer,
Checking out the centrosome.
2004,
Pubmed
Lowe,
Specificity determinants of recruitment peptides bound to phospho-CDK2/cyclin A.
2002,
Pubmed
Matsumoto,
A centrosomal localization signal in cyclin E required for Cdk2-independent S phase entry.
2004,
Pubmed
Mikule,
Loss of centrosome integrity induces p38-p53-p21-dependent G1-S arrest.
2007,
Pubmed
Moore,
Unmasking the S-phase-promoting potential of cyclin B1.
2003,
Pubmed
,
Xenbase
Peng,
Undamaged DNA transmits and enhances DNA damage checkpoint signals in early embryos.
2007,
Pubmed
,
Xenbase
Petri,
The crystal structure of human cyclin B.
2007,
Pubmed
,
Xenbase
Polyak,
Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals.
1994,
Pubmed
Raff,
The roles of Fzy/Cdc20 and Fzr/Cdh1 in regulating the destruction of cyclin B in space and time.
2002,
Pubmed
Rieder,
The centrosome in vertebrates: more than a microtubule-organizing center.
2001,
Pubmed
Rosenberg,
Overexpression of human cyclin A advances entry into S phase.
1995,
Pubmed
Russo,
Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex.
1996,
Pubmed
Schulman,
Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A.
1998,
Pubmed
Strausfeld,
Both cyclin A and cyclin E have S-phase promoting (SPF) activity in Xenopus egg extracts.
1996,
Pubmed
,
Xenbase
Su,
Promiscuity rules? The dispensability of cyclin E and Cdk2.
2004,
Pubmed
Swenson,
The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes.
1986,
Pubmed
,
Xenbase
Toyoshima,
p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21.
1994,
Pubmed
Turner,
Expression of achaete-scute homolog 3 in Xenopus embryos converts ectodermal cells to a neural fate.
1994,
Pubmed
,
Xenbase
Wakefield,
Centrosomes have a role in regulating the destruction of cyclin B in early Drosophila embryos.
2000,
Pubmed
Wiese,
Microtubule nucleation: gamma-tubulin and beyond.
2006,
Pubmed
