Many functions of Hsp90 are dependent on its association with co chaperone proteins. Co chaperones mediate various aspects of Hsp90 function, including the association of Hsp90 with client Perifosine proteins http://www.selleckchem.com/products/brefeldin-a.html and Kyprolis the regulation of Hsp90 ATPase activity. Cyclophilin 40, FK506 binding protein 51, and FKBP52 are members of Inhibitors,Modulators,Libraries the immunophilin fam ily of Hsp90 co chaperones. This family is best charac terized for its association with Hsp90 steroid hormone receptor complexes containing client proteins such as the glucocorticoid, estrogen, progesterone, and androgen receptors. The individual immunophilin family members show some Inhibitors,Modulators,Libraries preference for specific hormone receptors, and they can both antagonize and promote the transcription mediated by these receptors.
Inhibitors,Modulators,Libraries For ex ample, FKBP51 inhibits the transcriptional activity of the glucocorticoid Inhibitors,Modulators,Libraries receptor, while FKBP52 is import ant for promoting the transcriptional activity Inhibitors,Modulators,Libraries Inhibitors,Modulators,Libraries Inhibitors,Modulators,Libraries of this re ceptor. In addition to steroid hormone receptors, immunophilin co chaperones have been found to complex with the Lck and Fes tyro sine kinases. As well, Inhibitors,Modulators,Libraries the expression and activity of ecto pically expressed v Src oncoprotein in Saccharomyces cerevisiae is dependent on the Cyp40 homolog, Cpr7. Immunophilin co chaperones are important in can cer, as Cyp40 and FKBP51 have been shown to promote the proliferation of androgen dependent and androgen independent prostate cancer cell lines.
We identified Cyp40 Inhibitors,Modulators,Libraries in a mass spectrometry screen Inhibitors,Modulators,Libraries designed to identify proteins regulated by the JunB tran scription factor in ALK ALCL.
JunB is an AP 1 family transcription factor that is highly expressed in ALK ALCL, and has been Inhibitors,Modulators,Libraries shown to promote the proliferation of the Karpas 299 ALK ALCL cell line. This transcription factor also promotes the expression of CD30 and the cytotoxic protein, Granzyme B, in ALK ALCL, which are phenotypic characteristics of this lymphoma. Inhibitors,Modulators,Libraries Since co chaperone proteins are important for Hsp90 function, and Hsp90 activity is critical in ALK ALCL, we were intrigued by our observation that JunB might promote the expression of Cyp40 in ALK ALCL.
buy inhibitor In this study, Inhibitors,Modulators,Libraries we examined whether the expression of the immunophilin co Inhibitors,Modulators,Libraries chaperones was regulated by onco genic signalling in ALK ALCL.
We also investigated whether the immunophilin co chaperone proteins were important for the viability of ALK ALCL cell lines. We found that NPM ALK induced the transcription of two immunophilin family co chaperones, Cyp40 and FKBP52, Inhibitors,Modulators,Libraries but that only Cyp40 transcription was pro moted by JunB. In addition, knocking down the expres sion of Cyp40, but not FKBP51 or FKBP52, reduced the viability of thoroughly ALK ALCL cell lines. However, knock down of the immunophilin proteins did not appear to regulate method NPM ALK stability or activation.