Linked Life Data

16339216

Source:http://linkedlifedata.com/resource/pubmed/id/16339216

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-1-12
pubmed:abstractText
Tuberous sclerosis complex (TSC) is a tumor suppressor gene syndrome caused by mutations in TSC1 and TSC2. Hamartin and tuberin, the products of TSC1 and TSC2, respectively, form heterodimers and inhibit the mammalian target of rapamycin. Previously, we have shown that hamartin is phosphorylated by CDC2/cyclin B1 during the G(2)/M phase of the cell cycle. Here, we report that hamartin is localized to the centrosome and that phosphorylated hamartin and phosphorylated tuberin co-immunoprecipitate with the mitotic kinase Plk1. Plk1 interacts with the N-terminus of hamartin (amino acids 1-880), which contains two potential Plk1-binding sites (T310 and S332). Phosphorylated hamartin interacts with Plk1 independent of tuberin with all three proteins present in a complex. A non-phosphorylatable hamartin mutant with an alanine substitution at residue T310 does not interact with Plk1, whereas a non-phosphorylatable hamartin mutant at residue S332 in conjunction with alanine mutations at the other CDC2/cyclin B1 sites (T417, S584 and T1047) does not impact hamartin binding to Plk1. Hamartin negatively regulates the protein levels of Plk1. Finally, Tsc1(-/-) mouse embryonic fibroblasts (MEFs) have increased number of centrosomes and increased DNA content, compared to Tsc1(+/+) cells. Both phenotypes are rescued after pre-treatment with the mTOR inhibitor rapamycin. RNAi inhibition of Plk1 in Tsc1(-/-) MEFs failed to rescue the increased centrosome number phenotype. These data reveal a novel subcellular localization for hamartin and a novel interaction partner for the hamartin/tuberin complex and implicate hamartin and mTOR in the regulation of centrosome duplication.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
287-97
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:16339216-Animals, pubmed-meshheading:16339216-Cell Cycle Proteins, pubmed-meshheading:16339216-Cell Fractionation, pubmed-meshheading:16339216-Cell Line, pubmed-meshheading:16339216-Centrosome, pubmed-meshheading:16339216-Cercopithecus aethiops, pubmed-meshheading:16339216-Flow Cytometry, pubmed-meshheading:16339216-Humans, pubmed-meshheading:16339216-Immunoblotting, pubmed-meshheading:16339216-Immunoprecipitation, pubmed-meshheading:16339216-Mice, pubmed-meshheading:16339216-Microscopy, Fluorescence, pubmed-meshheading:16339216-Multiprotein Complexes, pubmed-meshheading:16339216-Mutation, pubmed-meshheading:16339216-Phosphorylation, pubmed-meshheading:16339216-Protein Binding, pubmed-meshheading:16339216-Protein-Serine-Threonine Kinases, pubmed-meshheading:16339216-Proto-Oncogene Proteins, pubmed-meshheading:16339216-RNA Interference, pubmed-meshheading:16339216-Sirolimus, pubmed-meshheading:16339216-Tumor Suppressor Proteins
pubmed:year
2006
pubmed:articleTitle
Hamartin, the tuberous sclerosis complex 1 gene product, interacts with polo-like kinase 1 in a phosphorylation-dependent manner.
pubmed:affiliation
Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural