Structural highlights
Function
PSME3_HUMAN Subunit of the 11S REG-gamma (also called PA28-gamma) proteasome regulator, a doughnut-shaped homoheptamer which associates with the proteasome. 11S REG-gamma activates the trypsin-like catalytic subunit of the proteasome but inhibits the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits. Facilitates the MDM2-p53/TP53 interaction which promotes ubiquitination- and MDM2-dependent proteasomal degradation of p53/TP53, limiting its accumulation and resulting in inhibited apoptosis after DNA damage. May also be involved in cell cycle regulation. Mediates CCAR2 and CHEK2-dependent SIRT1 inhibition (PubMed:25361978).[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
The PA28 family proteasome activators play important roles in regulating proteasome activities. Though the three paralogs (PA28alpha, PA28beta, and PA28gamma) are similar in terms of primary sequence, they show significant differences in expression pattern, cellular localization and most importantly, biological functions. While PA28alphabeta is responsible for promoting peptidase activity of proteasome to facilitate MHC-I antigen processing, but unable to promote protein degradation, PA28gamma is well-known to not only promote peptidase activity but also proteolytic activity of proteasome. However, why this paralog has the unique function remains elusive. Previous structural studies have mainly focused on mammalian PA28alpha, PA28beta and PA28alphabeta heptamers, while structural studies on mammalian PA28gamma of atomic resolution are still absent to date. In the present work, we determined the Cryo-EM structure of the human PA28gamma heptamer at atomic resolution, revealing interesting unique structural features that may hint our understanding the functional mechanisms of this proteasome activator.
Atomic resolution Cryo-EM structure of human proteasome activator PA28gamma.,Chen DD, Hao J, Shen CH, Deng XM, Yun CH Int J Biol Macromol. 2022 Oct 31;219:500-507. doi: , 10.1016/j.ijbiomac.2022.07.246. Epub 2022 Aug 4. PMID:35932807[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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References
- ↑ Li J, Gao X, Joss L, Rechsteiner M. The proteasome activator 11 S REG or PA28: chimeras implicate carboxyl-terminal sequences in oligomerization and proteasome binding but not in the activation of specific proteasome catalytic subunits. J Mol Biol. 2000 Jun 9;299(3):641-54. doi: 10.1006/jmbi.2000.3800. PMID:10835274 doi:http://dx.doi.org/10.1006/jmbi.2000.3800
- ↑ Wilk S, Chen WE, Magnusson RP. Properties of the nuclear proteasome activator PA28gamma (REGgamma). Arch Biochem Biophys. 2000 Nov 15;383(2):265-71. doi: 10.1006/abbi.2000.2086. PMID:11185562 doi:http://dx.doi.org/10.1006/abbi.2000.2086
- ↑ Li J, Gao X, Ortega J, Nazif T, Joss L, Bogyo M, Steven AC, Rechsteiner M. Lysine 188 substitutions convert the pattern of proteasome activation by REGgamma to that of REGs alpha and beta. EMBO J. 2001 Jul 2;20(13):3359-69. doi: 10.1093/emboj/20.13.3359. PMID:11432824 doi:http://dx.doi.org/10.1093/emboj/20.13.3359
- ↑ Gao X, Li J, Pratt G, Wilk S, Rechsteiner M. Purification procedures determine the proteasome activation properties of REG gamma (PA28 gamma). Arch Biochem Biophys. 2004 May 15;425(2):158-64. doi: 10.1016/j.abb.2004.03.021. PMID:15111123 doi:http://dx.doi.org/10.1016/j.abb.2004.03.021
- ↑ Zhang Z, Zhang R. Proteasome activator PA28 gamma regulates p53 by enhancing its MDM2-mediated degradation. EMBO J. 2008 Mar 19;27(6):852-64. doi: 10.1038/emboj.2008.25. Epub 2008 Feb 28. PMID:18309296 doi:http://dx.doi.org/10.1038/emboj.2008.25
- ↑ Magni M, Ruscica V, Buscemi G, Kim JE, Nachimuthu BT, Fontanella E, Delia D, Zannini L. Chk2 and REGgamma-dependent DBC1 regulation in DNA damage induced apoptosis. Nucleic Acids Res. 2014 Dec 1;42(21):13150-60. doi: 10.1093/nar/gku1065. Epub, 2014 Oct 31. PMID:25361978 doi:http://dx.doi.org/10.1093/nar/gku1065
- ↑ Realini C, Jensen CC, Zhang Z, Johnston SC, Knowlton JR, Hill CP, Rechsteiner M. Characterization of recombinant REGalpha, REGbeta, and REGgamma proteasome activators. J Biol Chem. 1997 Oct 10;272(41):25483-92. doi: 10.1074/jbc.272.41.25483. PMID:9325261 doi:http://dx.doi.org/10.1074/jbc.272.41.25483
- ↑ Chen DD, Hao J, Shen CH, Deng XM, Yun CH. Atomic resolution Cryo-EM structure of human proteasome activator PA28gamma. Int J Biol Macromol. 2022 Aug 4;219:500-507. doi: 10.1016/j.ijbiomac.2022.07.246. PMID:35932807 doi:http://dx.doi.org/10.1016/j.ijbiomac.2022.07.246
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