Linked Life Data

21088498

Source:http://linkedlifedata.com/resource/pubmed/id/21088498

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2011-1-20
pubmed:abstractText
?Np63?, the dominant negative isoform of the p63 family is an essential survival factor in head and neck squamous cell carcinoma. This isoform has been shown to be down regulated in response to several DNA damaging agents, thereby enabling an effective cellular response to genotoxic agents. Here, we identify a key molecular mechanism underlying the regulation of ?Np63? expression in response to extrinsic stimuli, such as chemotherapeutic agents. We show that ?Np63? interacts with NF-?? in presence of cisplatin. We find that NF-?? promotes ubiquitin-mediated proteasomal degradation of ?Np63?. Chemotherapy-induced stimulation of NF-?? leads to degradation of ?Np63? and augments trans-activation of p53 family-induced genes involved in the cellular response to DNA damage. Conversely, inhibition of NF-?? with siRNA-mediated silencing NF-?? expression attenuates chemotherapy induced degradation of ?Np63? . These data demonstrate that NF-?? plays an essential role in regulating ?Np63? in response to extrinsic stimuli. Our findings suggest that the activation of NF-?? may be a mechanism by which levels of ?Np63? are reduced, thereby rendering the cells susceptible to cell death in the face of cellular stress or DNA damage.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4841-7
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Regulation of ?Np63? by NF??.
pubmed:affiliation
Department of Otolaryngology-Head and Neck Surgery, Division of Head and Neck Cancer Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural