Linked Life Data

17546054

Source:http://linkedlifedata.com/resource/pubmed/id/17546054

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
52
pubmed:dateCreated
2007-11-16
pubmed:abstractText
The 14-3-3sigma, upregulated by p53 in response to DNA damage, can have a positive-feedback impact driving p53 activities and is a human cancer epithelial marker downregulated in various tumors. However, the precise roles of 14-3-3sigma during tumorigenesis are not well characterized. Here, we show that 14-3-3sigma is a critical regulator of murine double minute oncogene (MDM2). 14-3-3sigma interacts with MDM2 at the RING domain. The C-terminal region of 14-3-3sigma binds to MDM2 very efficiently. Importantly, 14-3-3sigma overexpression leads to destabilization of MDM2 through enhancing MDM2 self-ubiquitination and accelerating turnover rate. Conversely, loss of 14-3-3sigma results in a significant increase in MDM2 protein. Moreover, live-cell images indicated that 14-3-3sigma can affect the location of MDM2 from the nucleus to the cytoplasm, and that MDM2-mediated cytoplasmic localization of p53 can be reversed by the presence of 14-3-3sigma. Significantly, we further showed that 14-3-3sigma causes MDM2 downregulation, thereby stabilizing p53 and inhibiting tumor growth in animal tumors. Also, 14-3-3sigma blocks MDM2-mediated retinoblastoma degradation and p53 NEDDylation. Our results provide evidence that 14-3-3sigma is a pivotal MDM2 regulator involved in blocking a variety of activities of MDM2.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7355-62
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Roles for negative cell regulator 14-3-3sigma in control of MDM2 activities.
pubmed:affiliation
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural