Linked Life Data

16118210

Source:http://linkedlifedata.com/resource/pubmed/id/16118210

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
2005-10-17
pubmed:abstractText
Cell cycle progression is regulated by cyclin-dependent kinases (CDKs), cyclins, and CDK inhibitors. In the frog, Xenopus laevis, the CDK inhibitor p27(Xic1) (Xic1) inhibits DNA synthesis by negatively regulating CDK2-cyclin E. Using the frog egg extract as a model system for the study of Xic1, studies have demonstrated that Xic1 protein levels are regulated by nuclear ubiquitination and proteolysis. To characterize the molecular mechanism that regulates Xic1 turnover, we have identified the minimal sequences of Xic1 that are necessary and sufficient for its nuclear ubiquitination and degradation. Using deletion mutagenesis, our studies indicated that the C-terminal 50 amino acids of Xic1 are critical for its proteolysis beyond a role in nuclear transport. Replacement of the Xic1 C terminus with the SV40 nuclear localization sequence resulted in the nuclear localization of Xic1 but not its ubiquitination or degradation. Our deletion studies also indicated that the CDK2-cyclin binding domain of Xic1 is important for its efficient retention in the nucleus. Further deletion analyses identified at least 3 lysine residues within the Xic1 C terminus that are targeted for specific ubiquitination. Importantly, our studies demonstrated that the Xic1 C-terminal 50 amino acids can serve as a nuclear degradation signal when fused to a stable heterologous nuclear protein. Moreover, a 30-amino-acid region within the C terminus of Xic1 can serve as a nuclear ubiquitination signal. To address the role of phosphorylation on Xic1 turnover, all the potential phosphorylation sites within the C-terminal 50 amino acids of Xic1 were mutated to alanine to prevent possible phosphorylation. This resulted in a Xic1 protein that was nevertheless degraded in a manner similar to wild-type Xic1, suggesting that phosphorylation of Xic1 is not critical for its nuclear ubiquitination or proteolysis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35290-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16118210-Active Transport, Cell Nucleus, pubmed-meshheading:16118210-Amino Acid Motifs, pubmed-meshheading:16118210-Animals, pubmed-meshheading:16118210-Cell Cycle, pubmed-meshheading:16118210-Cell Nucleus, pubmed-meshheading:16118210-Cyclin-Dependent Kinase 2, pubmed-meshheading:16118210-Cyclin-Dependent Kinase Inhibitor p27, pubmed-meshheading:16118210-Cytoplasm, pubmed-meshheading:16118210-DNA, pubmed-meshheading:16118210-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:16118210-Gene Deletion, pubmed-meshheading:16118210-Glutathione Transferase, pubmed-meshheading:16118210-Immunoprecipitation, pubmed-meshheading:16118210-Lysine, pubmed-meshheading:16118210-Mutagenesis, pubmed-meshheading:16118210-Phosphorylation, pubmed-meshheading:16118210-Point Mutation, pubmed-meshheading:16118210-Protein Binding, pubmed-meshheading:16118210-Protein Biosynthesis, pubmed-meshheading:16118210-Protein Structure, Tertiary, pubmed-meshheading:16118210-Time Factors, pubmed-meshheading:16118210-Transcription, Genetic, pubmed-meshheading:16118210-Ubiquitin, pubmed-meshheading:16118210-Xenopus Proteins, pubmed-meshheading:16118210-Xenopus laevis
pubmed:year
2005
pubmed:articleTitle
The C-terminal domain of the Xenopus cyclin-dependent kinase inhibitor, p27Xic1, is both necessary and sufficient for phosphorylation-independent proteolysis.
pubmed:affiliation
Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural