Linked Life Data

17121812

Source:http://linkedlifedata.com/resource/pubmed/id/17121812

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-1-29
pubmed:abstractText
Caspase 8/10-associated RING proteins (CARPs) are a recently described family of protein ubiquitin ligases that interact with and negatively regulate death receptor-mediated apoptosis. Because CARPs are overexpressed in cancer and their silencing reduces cell viability and sensitizes tumor cells to chemotherapeutic agents, we investigated their relationship to p53 tumor suppressor signaling. p53 is a major determinant of chemosensitivity, and its levels are increased following DNA damage through N-terminal phosphorylation and inhibition of degradation. Although p53 is well known to be negatively regulated by several ubiquitin ligases including MDM2, none are known to target phosphorylated p53 for degradation. CARPs physically interact with and ubiquitinate p53, targeting it for degradation in the absence of MDM2. Serine 20-phosphorylated p53 is also ubiquitinated by CARPs. CARP silencing stimulates p53 expression and promotes downstream effects, including transcriptional activation and tumor suppression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3273-81
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
CARPs are ubiquitin ligases that promote MDM2-independent p53 and phospho-p53ser20 degradation.
pubmed:affiliation
Laboratory of Molecular Oncology and Cell Cycle Regulation, Department of Medicine, The Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, PA 19104, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural