| First Author | Um JW | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 47 | Pages | 36434-46 |
| PubMed ID | 20843792 | Mgi Jnum | J:166859 |
| Mgi Id | MGI:4849895 | Doi | 10.1074/jbc.M110.133777 |
| Citation | Um JW, et al. (2010) ASK1 negatively regulates the 26 S proteasome. J Biol Chem 285(47):36434-46 |
| abstractText | The 26 S proteasome, composed of the 20 S core and 19 S regulatory particle, plays a central role in ubiquitin-dependent proteolysis. Disruption of this process contributes to the pathogenesis of the various diseases; however, the mechanisms underlying the regulation of 26 S proteasome activity remain elusive. Here, cell culture experiments and in vitro assays demonstrated that apoptosis signal-regulating kinase 1 (ASK1), a member of the MAPK kinase kinase family, negatively regulated 26 S proteasome activity. Immunoprecipitation/Western blot analyses revealed that ASK1 did not interact with 20 S catalytic core but did interact with ATPases making up the 19 S particle, which is responsible for recognizing polyubiquitinated proteins, unfolding them, and translocating them into the 20 S catalytic core in an ATP-dependent process. Importantly, ASK1 phosphorylated Rpt5, an AAA ATPase of the 19 S proteasome, and inhibited its ATPase activity, an effect that may underlie the ability of ASK1 to inhibit 26 S proteasome activity. The current findings point to a novel role for ASK1 in the regulation of 26 S proteasome and offer new strategies for treating human diseases caused by proteasome malfunction. |
