Linked Life Data

12902986

Source:http://linkedlifedata.com/resource/pubmed/id/12902986

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
32
pubmed:dateCreated
2003-8-6
pubmed:abstractText
Papillary renal cell carcinomas are associated with chromosomal translocations involving the helix-loop-helix leucine-zipper region of the TFE3 gene on the X chromosome. These translocations lead to the expression of TFE3 chimeras of PRCC, RCC17, NonO and PSF (PTB-associated splicing factor). In this study, we explored the role of PSF-TFE3 fusion protein in mediating cell transformation. Unlike wild-type TFE3 or PSF, which are nuclear proteins, PSF-TFE3 is not a nuclear protein and is targeted to the endosomal compartment. Although PSF-TFE3 has no effect on the nuclear localization of wild-type PSF, it sequesters wild-type TFE3 as well as p53 in the extranuclear compartment leading to functionally null p53 and TFE3 cells. In UOK-145 papillary renal carcinoma cells, which endogenously express PSF-TFE3, siRNA complementary to the PSF-TFE3 fusion junction leads to a reduction in PSF-TFE3 and redistribution of endogenous TFE3 and p53 from the cytoplasmic compartment to the nucleus. Our results indicate that PSF-TFE3 acts through a novel mechanism, and exports TFE3, p53 and possibly other factors from the nucleus to the cytoplasm for degradation leading to the transformed phenotype. Thus, PSF-TFE3 is a promising target for the treatment for a subset of renal cell carcinomas.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5031-44
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
PSF-TFE3 oncoprotein in papillary renal cell carcinoma inactivates TFE3 and p53 through cytoplasmic sequestration.
pubmed:affiliation
Departments of Pharmacology and Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. mukul.mathur@med.nyu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.