Linked Life Data

21383157

Source:http://linkedlifedata.com/resource/pubmed/id/21383157

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2011-3-23
pubmed:abstractText
The large tumor suppressor 1 (LATS1) is a serine/threonine kinase and tumor suppressor found down-regulated in a broad spectrum of human cancers. LATS1 is a central player of the emerging Hippo-LATS suppressor pathway, which plays important roles in cell proliferation, apoptosis, and stem cell differentiation. Despite the ample data supporting a role for LATS1 in tumor suppression, how LATS1 is regulated at the molecular level remains largely unknown. In this study, we have identified Itch, a HECT class E3 ubiquitin ligase, as a unique binding partner of LATS1. Itch can complex with LATS1 both in vitro and in vivo through the PPxY motifs of LATS1 and the WW domains of Itch. Significantly, we found that overexpression of Itch promoted LATS1 degradation by polyubiquitination through the 26S proteasome pathway. On the other hand, knockdown of endogenous Itch by shRNAs provoked stabilization of endogenous LATS1 proteins. Finally, through several functional assays, we also revealed that change of Itch abundance alone is sufficient for altering LATS1-mediated downstream signaling, negative regulation of cell proliferation, and induction of apoptosis. Taking these data together, our study identifies E3 ubiquitin ligase Itch as a unique negative regulator of LATS1 and presents a possibility of targeting LATS1/Itch interaction as a therapeutic strategy in cancer.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4870-5
pubmed:dateRevised
2011-9-23
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Itch E3 ubiquitin ligase regulates large tumor suppressor 1 stability [corrected].
pubmed:affiliation
Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada K7L 3N6.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't