Phone: +46 (0)31 786 2594
Visiting address: Medicinaregatan 9C
Proteases play a key role in various biological processes. Deubiquitinating enzymes (DUBs) constitute one of the largest classes of proteases and are crucial players in the ubiquitin-proteasome system and in autophagy. These pathways regulating cellular protein turnover have been implicated in several diseases, including neurodegenerative disorders and cancers. The work of the Kvint group is aimed at elucidating the role of DUBs in gene expression and protein quality control. Specifically, we are interested in investigating the molecular mechanisms and via what pathways the DUB, Ubp3, regulates these processes in Saccharomyces cerevisiae.
We have found that Ubp3 deubiquitinates RNAPII both in vivo and in vitro. By classic genetic and biochemical characterizations we have shown that cells lacking the UBP3 gene have defects in transcription, an altered DNA-damage response, and that Ubp3 can be purified with RNAPII, Def1 and the elongation factors Spt5 and TFIIF. Presently we are investigating how this occurs in more detail.
In addition, cells lacking UBP3 turn out to have a delayed and altered response to heat shock stress compared to wild type cells. For instance, data show that Ubp3 mutants are slow in dissolving heat induced protein aggregates. Over-expression of Ubp3 can suppress heat sensitivity of cells devoid of the heat shock proteins Ssa1 and Ssa2, with which Ubp3 copurifies. Currently we are investigating the mechanisms behind this by asking questions like: Is the ability to restore aggregated proteins to native structure and function a problem for UBP3 mutants? Are UBP3 mutants deficient in pathways that degrade aberrant proteins? If so, what is the molecular mechanisms behind this and what other factors/pathways are involved?