| Structural highlights
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Function
[RPN9_YEAST] Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. [RPN6_YEAST] Component of the lid subcomplex of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. In the complex, RPN6 is required for proteasome assembly.[1] [2] [3] [RPN11_YEAST] Acts as a regulatory subunit of the 26 proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins.[4] [SEM1_YEAST] Versatile protein that might stabilize multiple protein complexes involved in diverse pathways. Subunit of the 26S proteasome which plays a role in ubiquitin-dependent proteolysis. Associates also with the TREX-2 complex that is required for transcription-coupled mRNA export, and the COP9 signalosome, which is involved in deneddylation.[5] [6] [RPN5_YEAST] Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins.[7] [RPN12_YEAST] Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. Necessary for activation of the CDC28 kinase. [RPN3_YEAST] Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins. [RPN7_YEAST] Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins (By similarity). [RPN8_YEAST] Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins.[8]
Publication Abstract from PubMed
The 26S proteasome is responsible for the selective, ATP-dependent degradation of polyubiquitinated cellular proteins. Removal of ubiquitin chains from targeted substrates at the proteasome is a prerequisite for substrate processing and is accomplished by Rpn11, a deubiquitinase within the 'lid' sub-complex. Prior to the lid's incorporation into the proteasome, Rpn11 deubiquitinase activity is inhibited to prevent unwarranted deubiquitination of polyubiquitinated proteins. Here we present the atomic model of the isolated lid sub-complex, as determined by cryo-electron microscopy at 3.5 A resolution, revealing how Rpn11 is inhibited through its interaction with a neighboring lid subunit, Rpn5. Through mutagenesis of specific residues, we describe the network of interactions that are required to stabilize this inhibited state. These results provide significant insight into the intricate mechanisms of proteasome assembly, outlining the substantial conformational rearrangements that occur during incorporation of the lid into the 26S holoenzyme, which ultimately activates the deubiquitinase for substrate degradation.
Atomic structure of the 26S proteasome lid reveals the mechanism of deubiquitinase inhibition.,Dambacher CM, Worden EJ, Herzik MA, Martin A, Lander GC Elife. 2016 Jan 8;5. pii: e13027. doi: 10.7554/eLife.13027. PMID:26744777[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Saito A, Watanabe TK, Shimada Y, Fujiwara T, Slaughter CA, DeMartino GN, Tanahashi N, Tanaka K. cDNA cloning and functional analysis of p44.5 and p55, two regulatory subunits of the 26S proteasome. Gene. 1997 Dec 12;203(2):241-50. PMID:9426256
- ↑ Santamaria PG, Finley D, Ballesta JP, Remacha M. Rpn6p, a proteasome subunit from Saccharomyces cerevisiae, is essential for the assembly and activity of the 26 S proteasome. J Biol Chem. 2003 Feb 28;278(9):6687-95. Epub 2002 Dec 16. PMID:12486135 doi:10.1074/jbc.M209420200
- ↑ Isono E, Saito N, Kamata N, Saeki Y, Toh-E A. Functional analysis of Rpn6p, a lid component of the 26 S proteasome, using temperature-sensitive rpn6 mutants of the yeast Saccharomyces cerevisiae. J Biol Chem. 2005 Feb 25;280(8):6537-47. Epub 2004 Dec 15. PMID:15611133 doi:10.1074/jbc.M409364200
- ↑ Chen L, Romero L, Chuang SM, Tournier V, Joshi KK, Lee JA, Kovvali G, Madura K. Sts1 plays a key role in targeting proteasomes to the nucleus. J Biol Chem. 2011 Jan 28;286(4):3104-18. doi: 10.1074/jbc.M110.135863. Epub 2010 , Nov 12. PMID:21075847 doi:10.1074/jbc.M110.135863
- ↑ Faza MB, Kemmler S, Jimeno S, Gonzalez-Aguilera C, Aguilera A, Hurt E, Panse VG. Sem1 is a functional component of the nuclear pore complex-associated messenger RNA export machinery. J Cell Biol. 2009 Mar 23;184(6):833-46. doi: 10.1083/jcb.200810059. Epub 2009 Mar, 16. PMID:19289793 doi:http://dx.doi.org/10.1083/jcb.200810059
- ↑ Sone T, Saeki Y, Toh-e A, Yokosawa H. Sem1p is a novel subunit of the 26 S proteasome from Saccharomyces cerevisiae. J Biol Chem. 2004 Jul 2;279(27):28807-16. Epub 2004 Apr 26. PMID:15117943 doi:http://dx.doi.org/10.1074/jbc.M403165200
- ↑ Saito A, Watanabe TK, Shimada Y, Fujiwara T, Slaughter CA, DeMartino GN, Tanahashi N, Tanaka K. cDNA cloning and functional analysis of p44.5 and p55, two regulatory subunits of the 26S proteasome. Gene. 1997 Dec 12;203(2):241-50. PMID:9426256
- ↑ Glickman MH, Rubin DM, Fried VA, Finley D. The regulatory particle of the Saccharomyces cerevisiae proteasome. Mol Cell Biol. 1998 Jun;18(6):3149-62. PMID:9584156
- ↑ Dambacher CM, Worden EJ, Herzik MA, Martin A, Lander GC. Atomic structure of the 26S proteasome lid reveals the mechanism of deubiquitinase inhibition. Elife. 2016 Jan 8;5. pii: e13027. doi: 10.7554/eLife.13027. PMID:26744777 doi:http://dx.doi.org/10.7554/eLife.13027
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