Linked Life Data

15855168

Source:http://linkedlifedata.com/resource/pubmed/id/15855168

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2005-6-13
pubmed:abstractText
Previous reports have shown that the N terminus of Cdt1 is required for its degradation during S phase (Li, X., Zhao, Q., Liao, R., Sun, P., and Wu, X. (2003) J. Biol. Chem. 278, 30854-30858; Nishitani, H., Lygerou, Z., and Nishimoto, T. (2004) J. Biol. Chem. 279, 30807-30816). The stabilization was attributed to deletion of the cyclin binding motif (Cy motif), which is required for its phosphorylation by cyclin-dependent kinases. Phosphorylated Cdt1 is subsequently recognized by the F-box protein Skp2 and targeted for proteasomal mediated degradation. Using phosphopeptide mapping and mutagenesis studies, we found that threonine 29 within the N terminus of Cdt1 is phosphorylated by Cdk2 and required for interaction with Skp2. However, threonine 29 and the Cy motif are not necessary for proteolysis of Cdt1 during S phase. Mutants of Cdt1 that do not stably associate with Skp2 or cyclins are still degraded in S phase to the same extent as wild type Cdt1, indicating that other determinants within the N terminus of Cdt1 are required for degrading Cdt1. We localized the region necessary for Cdt1 degradation to the first 32 residues. Overexpression of stable forms of Cdt1 significantly delayed entry into and completion of S phase, suggesting that failure to degrade Cdt1 prevents normal progression through S phase. In contrast, Cdt1 mutants that fail to interact with Skp2 and cyclins progress through S phase with similar kinetics as wild type Cdt1 but stimulate the re-replication caused by overexpressing Cdt1. Therefore, a Skp2-independent pathway that requires the N-terminal 32 residues of Cdt1 is critical for the degradation of Cdt1 in S phase, and this degradation is necessary for the optimum progression of cells through S phase.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23416-23
pubmed:dateRevised
2011-10-3
pubmed:meshHeading
pubmed-meshheading:15855168-Amino Acid Motifs, pubmed-meshheading:15855168-Amino Acid Sequence, pubmed-meshheading:15855168-Cell Cycle, pubmed-meshheading:15855168-Cell Cycle Proteins, pubmed-meshheading:15855168-Cell Line, pubmed-meshheading:15855168-Cell Separation, pubmed-meshheading:15855168-DNA-Binding Proteins, pubmed-meshheading:15855168-Flow Cytometry, pubmed-meshheading:15855168-HeLa Cells, pubmed-meshheading:15855168-Humans, pubmed-meshheading:15855168-Immunoblotting, pubmed-meshheading:15855168-Kinetics, pubmed-meshheading:15855168-Mass Spectrometry, pubmed-meshheading:15855168-Molecular Sequence Data, pubmed-meshheading:15855168-Mutagenesis, Site-Directed, pubmed-meshheading:15855168-Mutation, pubmed-meshheading:15855168-Nuclear Proteins, pubmed-meshheading:15855168-Peptide Mapping, pubmed-meshheading:15855168-Peptides, pubmed-meshheading:15855168-Phosphorylation, pubmed-meshheading:15855168-Plasmids, pubmed-meshheading:15855168-Point Mutation, pubmed-meshheading:15855168-Protein Binding, pubmed-meshheading:15855168-Protein Structure, Tertiary, pubmed-meshheading:15855168-S Phase, pubmed-meshheading:15855168-S-Phase Kinase-Associated Proteins, pubmed-meshheading:15855168-Threonine, pubmed-meshheading:15855168-Transfection
pubmed:year
2005
pubmed:articleTitle
Degradation of Cdt1 during S phase is Skp2-independent and is required for efficient progression of mammalian cells through S phase.
pubmed:affiliation
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural