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http://purl.uniprot.org/citations/22681779http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22681779http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22681779http://www.w3.org/2000/01/rdf-schema#comment"

Background

Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is a T cell lymphoma defined by the presence of chromosomal translocations involving the ALK tyrosine kinase gene. These translocations generate fusion proteins (e.g. NPM-ALK) with constitutive tyrosine kinase activity, which activate numerous signalling pathways important for ALK+ ALCL pathogenesis. The molecular chaperone heat shock protein-90 (Hsp90) plays a critical role in allowing NPM-ALK and other signalling proteins to function in this lymphoma. Co-chaperone proteins are important for helping Hsp90 fold proteins and for directing Hsp90 to specific clients; however the importance of co-chaperone proteins in ALK+ ALCL has not been investigated. Our preliminary findings suggested that expression of the immunophilin co-chaperone, Cyclophilin 40 (Cyp40), is up-regulated in ALK+ ALCL by JunB, a transcription factor activated by NPM-ALK signalling. In this study we examined the regulation of the immunophilin family of co-chaperones by NPM-ALK and JunB, and investigated whether the immunophilin co-chaperones promote the viability of ALK+ ALCL cell lines.

Methods

NPM-ALK and JunB were knocked-down in ALK+ ALCL cell lines with siRNA, and the effect on the expression of the three immunophilin co-chaperones: Cyp40, FK506-binding protein (FKBP) 51, and FKBP52 examined. Furthermore, the effect of knock-down of the immunophilin co-chaperones, either individually or in combination, on the viability of ALK+ ALCL cell lines and NPM-ALK levels and activity was also examined.

Results

We found that NPM-ALK promoted the transcription of Cyp40 and FKBP52, but only Cyp40 transcription was promoted by JunB. We also observed reduced viability of ALK+ ALCL cell lines treated with Cyp40 siRNA, but not with siRNAs directed against FKBP52 or FKBP51. Finally, we demonstrate that the decrease in the viability of ALK+ ALCL cell lines treated with Cyp40 siRNA does not appear to be due to a decrease in NPM-ALK levels or the ability of this oncoprotein to signal.

Conclusions

This is the first study demonstrating that the expression of immunophilin family co-chaperones is promoted by an oncogenic tyrosine kinase. Moreover, this is the first report establishing an important role for Cyp40 in lymphoma."xsd:string
http://purl.uniprot.org/citations/22681779http://purl.org/dc/terms/identifier"doi:10.1186/1471-2407-12-229"xsd:string
http://purl.uniprot.org/citations/22681779http://purl.org/dc/terms/identifier"doi:10.1186/1471-2407-12-229"xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/author"Lai R."xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/author"Lai R."xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/author"Ingham R.J."xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/author"Ingham R.J."xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/author"Pearson J.D."xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/author"Pearson J.D."xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/author"Bacani J.T."xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/author"Bacani J.T."xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/author"Mohammed Z."xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/author"Mohammed Z."xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/name"BMC Cancer"xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/name"BMC Cancer"xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/pages"229"xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/pages"229"xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/title"The heat shock protein-90 co-chaperone, Cyclophilin 40, promotes ALK-positive, anaplastic large cell lymphoma viability and its expression is regulated by the NPM-ALK oncoprotein."xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/title"The heat shock protein-90 co-chaperone, Cyclophilin 40, promotes ALK-positive, anaplastic large cell lymphoma viability and its expression is regulated by the NPM-ALK oncoprotein."xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/volume"12"xsd:string
http://purl.uniprot.org/citations/22681779http://purl.uniprot.org/core/volume"12"xsd:string
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