Linked Life Data

12837690

Source:http://linkedlifedata.com/resource/pubmed/id/12837690

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2003-7-2
pubmed:abstractText
The MITF/TFE subfamily of basic helix-loop-helix leucine-zipper (bHLH-LZ) transcription factors consists of four closely related members, TFE3, TFEB, TFEC and MITF, which can form both homo- and heterodimers. Previously, we demonstrated that in t(X;1)(p11;q21)-positive renal cell carcinomas (RCCs), the TFE3 gene on the X chromosome is disrupted and fused to the PRCC gene on chromosome 1. Here we show that in t(6;11)(p21;q13)-positive RCCs the TFEB gene on chromosome 6 is fused to the Alpha gene on chromosome 11. The AlphaTFEB fusion gene appears to contain all coding exons of the TFEB gene linked to 5' upstream regulatory sequences of the Alpha gene. Quantitative PCR analysis revealed that AlphaTFEB mRNA levels are up to 60-fold upregulated in primary tumor cells as compared with wild-type TFEB mRNA levels in normal kidney samples, resulting in a dramatic upregulation of TFEB protein levels. Additional transfection studies revealed that the TFEB protein encoded by the AlphaTFEB fusion gene is efficiently targeted to the nucleus. Based on these results we conclude that the RCC-associated t(6;11)(p21;q13) translocation leads to a dramatic transcriptional and translational upregulation of TFEB due to promoter substitution, thereby severely unbalancing the nuclear ratios of the MITF/TFE subfamily members. We speculate that this imbalance may lead to changes in the expression of downstream target genes, ultimately resulting in the development of RCC. Moreover, since this is the second MITF/TFE transcription factor that is involved in RCC development, our findings point towards a concept in which this bHLH-LZ subfamily may play a critical role in the regulation of (aberrant) renal cellular growth.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1661-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Upregulation of the transcription factor TFEB in t(6;11)(p21;q13)-positive renal cell carcinomas due to promoter substitution.
pubmed:affiliation
Department of Human Genetics, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands. r.kuiper@antrg.umcn.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't