Small-molecule inhibitors of HSP90 resulted in HSP90-bound loci producing more full-length transcripts and harbouring elongating phospho-forms of Pol II, thus providing evidence that HSP90 is functionally involved in Pol II pausing. Furthermore, various experiments showed physical and functional interactions between HSP90 and the NELF complex, including studies in vivo in D. melanogaster and in mouse and human cells. Demonstrating the physiological relevance of HSP90 in Pol II pausing, Sawarkar et al. found that HSP90 inhibition impaired the LPS-mediated target gene induction in D. melanogaster cells and mouse cells as well as ecdysone-induced pupation in D. melanogaster.

Given that Pol II pausing seems to have roles both in the immediate regulation of target gene expression and in the longer-term regulation of signal transduction protein levels, it will be interesting to see whether timecourses of HSP90 inhibition will allow the relative importance of these roles to be dissected.