PSMF1 explained

Proteasome inhibitor PI31 subunit is a protein that in humans is encoded by the PSMF1 gene.^{[1] [2]}

Function

The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. PSMF1 encodes a protein termed PI31 that binds to both 20S and 26S proteasomes. PI31 was originally identified by its ability to inhibit the hydrolysis of small synthetic peptides in a cell free assay, but it stimulates 26S proteasome activity both in vitro and in vivo.^{[3] [4]} PI31 can promote the assembly of 26S proteasomes from 19S and 20S sub-particles, and it also serves as an adapter to couple proteasomes with motor proteins to mediate fast axonal transport in neurons.^[5] Inactivation of PMSF1 in yeast, plants, fruit flies and mice attenuates protein degradation and stimulates accumulation of ubiquitinated protein aggregates. Furthermore, loss of PSMF1 function in mice causes progressive neuronal dysfunction, synaptic degeneration and eventually neuronal cell death.^[6] Alternative transcript variants have been identified for this gene.

Further reading

• Cho-Park PF . Proteasome regulation by ADP-ribosylation . Cell . 153 . 3 . 614-27 . Apr 2013 . 23622245 . 10.1016/j.cell.2013.03.040 . free . 3676968 .
• Yang BJ . Arabidopsis PROTEASOME REGULATOR1 is required for auxin-mediated suppression of proteasome activity and regulates auxin signalling . Nat Commun . 7 . 3 . 11388 . Apr 2016 . 27109828 . 10.1038/ncomms11388 . free . 4848511 .
• Goff SP . Death by deamination: a novel host restriction system for HIV-1 . Cell . 114 . 3 . 281–3 . Aug 2003 . 12914693 . 10.1016/S0092-8674(03)00602-0 . 16340355 . free .
• Minghetti L, Visentin S, Patrizio M, Franchini L, Ajmone-Cat MA, Levi G . Multiple actions of the human immunodeficiency virus type-1 Tat protein on microglial cell functions . Neurochemical Research . 29 . 5 . 965–78 . May 2004 . 15139295 . 10.1023/B:NERE.0000021241.90133.89 . 25323034 .
• Liou LY, Herrmann CH, Rice AP . HIV-1 infection and regulation of Tat function in macrophages . The International Journal of Biochemistry & Cell Biology . 36 . 9 . 1767–75 . Sep 2004 . 15183343 . 10.1016/j.biocel.2004.02.018 .
• Bannwarth S, Gatignol A . HIV-1 TAR RNA: the target of molecular interactions between the virus and its host . Current HIV Research . 3 . 1 . 61–71 . Jan 2005 . 15638724 . 10.2174/1570162052772924 .
• Gibellini D, Vitone F, Schiavone P, Re MC . HIV-1 tat protein and cell proliferation and survival: a brief review . The New Microbiologica . 28 . 2 . 95–109 . Apr 2005 . 16035254 .
• Hetzer C, Dormeyer W, Schnölzer M, Ott M . Decoding Tat: the biology of HIV Tat posttranslational modifications . Microbes and Infection / Institut Pasteur . 7 . 13 . 1364–9 . Oct 2005 . 16046164 . 10.1016/j.micinf.2005.06.003 . free .
• Peruzzi F . The multiple functions of HIV-1 Tat: proliferation versus apoptosis . Frontiers in Bioscience . 11 . 708–17 . 2006 . 16146763 . 10.2741/1829 . free .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–13 . Apr 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Seeger M, Ferrell K, Frank R, Dubiel W . HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation . The Journal of Biological Chemistry . 272 . 13 . 8145–8 . Mar 1997 . 9079628 . 10.1074/jbc.272.13.8145 . free .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–8 . Apr 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Madani N, Kabat D . An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the viral Vif protein . Journal of Virology . 72 . 12 . 10251–5 . Dec 1998 . 9811770 . 110608 . 10.1128/JVI.72.12.10251-10255.1998.
• Simon JH, Gaddis NC, Fouchier RA, Malim MH . Evidence for a newly discovered cellular anti-HIV-1 phenotype . Nature Medicine . 4 . 12 . 1397–400 . Dec 1998 . 9846577 . 10.1038/3987 . 25235070 .
• McCutchen-Maloney SL, Matsuda K, Shimbara N, Binns DD, Tanaka K, Slaughter CA, DeMartino GN . cDNA cloning, expression, and functional characterization of PI31, a proline-rich inhibitor of the proteasome . The Journal of Biological Chemistry . 275 . 24 . 18557–65 . Jun 2000 . 10764772 . 10.1074/jbc.M001697200 . free .
• Mulder LC, Muesing MA . Degradation of HIV-1 integrase by the N-end rule pathway . The Journal of Biological Chemistry . 275 . 38 . 29749–53 . Sep 2000 . 10893419 . 10.1074/jbc.M004670200 . free .
• Sheehy AM, Gaddis NC, Choi JD, Malim MH . Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein . Nature . 418 . 6898 . 646–50 . Aug 2002 . 12167863 . 10.1038/nature00939 . 2002Natur.418..646S . 4403228 .
• Zaiss DM, Standera S, Kloetzel PM, Sijts AJ . PI31 is a modulator of proteasome formation and antigen processing . Proceedings of the National Academy of Sciences of the United States of America . 99 . 22 . 14344–9 . Oct 2002 . 12374861 . 137886 . 10.1073/pnas.212257299 . 2002PNAS...9914344Z . free .
• Huang X, Seifert U, Salzmann U, Henklein P, Preissner R, Henke W, Sijts AJ, Kloetzel PM, Dubiel W . The RTP site shared by the HIV-1 Tat protein and the 11S regulator subunit alpha is crucial for their effects on proteasome function including antigen processing . Journal of Molecular Biology . 323 . 4 . 771–82 . Nov 2002 . 12419264 . 10.1016/S0022-2836(02)00998-1 .

Notes and References

1. Tanahashi N, Kawahara H, Murakami Y, Tanaka K . The proteasome-dependent proteolytic system . Molecular Biology Reports . 26 . 1–2 . 3–9 . Apr 1999 . 10363639 . 10.1023/A:1006909522731 . 38305744 .
2. Web site: Entrez Gene: PSMF1 proteasome (prosome, macropain) inhibitor subunit 1 (PI31).
3. Chu-Ping . M . Purification and characterization of a protein inhibitor of the 20S proteasome (macropain) . BBA . 1119 . 303-11 . 10.1016/0167-4838(92)90218-3 . 1312359.
4. Bader . Maya . A conserved F box regulatory complex controls proteasome activity in Drosophila . Cell . 2011 . 145 . 10.1016/j.cell.2011.03.021 . 21529711. 3108249 .
5. Liu . Kai . PI31 Is an Adaptor Protein for Proteasome Transport in Axons and Required for Synaptic Development . Dev Cell . 2019 . 50 . 509-524 . 10.1016/j.devcel.2019.06.009 . 31327739. 6702053 .
6. Minis . Adi . The proteasome regulator PI31 is required for protein homeostasis, synapse maintenance, and neuronal survival in mice . Proc Natl Acad Sci U S A . 2019 . 116 . 24639-24650 . 10.1073/pnas.1911921116 . 31754024. 6900516 .