PSMB10

Proteasome subunit beta type-10 as known as 20S proteasome subunit beta-2i is a protein that in humans is encoded by the PSMB10 gene.[5]

PSMB10
Identifiers
Aliases	PSMB10, LMP10, MECL1, beta2i, proteasome subunit beta 10, proteasome 20S subunit beta 10
External IDs	OMIM: 176847 MGI: 1096380 HomoloGene: 20616 GeneCards: PSMB10
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q22.1 Start 67,934,506 bp[1] End 67,936,864 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8 D3|8 53.06 cM Start 105,935,735 bp[2] End 105,938,444 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • endopeptidase activity • peptidase activity • GO:0001948 protein binding • threonine-type endopeptidase activity • hydrolase activity Cellular component • cytoplasm • cytosol • nucleoplasm • proteasome complex • cell nucleus • proteasome core complex • spermatoproteasome complex • proteasome core complex, beta-subunit complex Biological process • proteolysis • humoral immune response • proteolysis involved in cellular protein catabolic process • GO:0022415 viral process • protein deubiquitination • immune system process • post-translational modification • cell morphogenesis • proteasomal protein catabolic process • proteasomal ubiquitin-independent protein catabolic process • T cell proliferation • proteasome-mediated ubiquitin-dependent protein catabolic process • MAPK cascade • protein polyubiquitination • stimulatory C-type lectin receptor signaling pathway • antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent • regulation of cellular amino acid metabolic process • negative regulation of G2/M transition of mitotic cell cycle • anaphase-promoting complex-dependent catabolic process • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process • tumor necrosis factor-mediated signaling pathway • NIK/NF-kappaB signaling • Fc-epsilon receptor signaling pathway • regulation of mRNA stability • T cell receptor signaling pathway • transmembrane transport • Wnt signaling pathway, planar cell polarity pathway • regulation of transcription from RNA polymerase II promoter in response to hypoxia • interleukin-1-mediated signaling pathway • negative regulation of canonical Wnt signaling pathway • positive regulation of canonical Wnt signaling pathway • regulation of mitotic cell cycle phase transition • regulation of hematopoietic stem cell differentiation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5699	19171
Ensembl	ENSG00000205220	ENSMUSG00000031897
UniProt	P40306	O35955
RefSeq (mRNA)	NM_002801	NM_013640
RefSeq (protein)	NP_002792	NP_038668
Location (UCSC)	Chr 16: 67.93 – 67.94 Mb	Chr 8: 105.94 – 105.94 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

This protein has a major role in the immune system as part of an immunoproteasome that is primarily induced upon infection and formed by replacing constitutive beta subunits with inducible beta subunits which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation.[6] The immunoproteasome appears to have a pivotal role in modulating NFκB signaling.[7]

Structure

Gene

This gene PSMB10 encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. Proteolytic processing is required to generate a mature subunit. Expression of this gene is induced by gamma interferon, and this gene product replaces catalytic subunit beta2 (proteasome subunit beta type-7) in the immunoproteasome.[8] The human PSMB10 gene has 8 exons and locates at chromosome band 16q22.1.

Protein structure

The human protein proteasome subunit beta type-8 is 25 kDa in size and composed of 234 amino acids. The calculated theoretical pI of this protein is 6.07.

Complex assembly

Proteasome subunit beta type-10 is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta-2i, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. This protein contains "Trypsin-like" activity and is capable of cleaving after basic residues of peptide.[9] The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. The constitutive subunit beta1, beta2, and beta 5 (systematic nomenclature) can be replaced by their inducible counterparts beta1i, 2i, and 5i when cells are under the treatment of interferon-γ. The resulting proteasome complex becomes the so-called immunoproteasome. An essential function of the modified proteasome complex, the immunoproteasome, is the processing of numerous MHC class-I restricted T cell epitopes.[10]

The proteasome is a multicatalytic proteinase complex with a highly ordered 20S core structure. This barrel-shaped core structure is composed of 4 axially stacked rings of 28 non-identical subunits: the two end rings are each formed by 7 alpha subunits, and the two central rings are each formed by 7 beta subunits. Three beta subunits (beta1, beta2, beta5) each contains a proteolytic active site and has distinct substrate preferences. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway.[11][12]

Function

Protein functions are supported by its tertiary structure and its interaction with associating partners. As one of 28 subunits of 20S proteasome, protein proteasome subunit beta type-2 contributes to form a proteolytic environment for substrate degradation. Evidences of the crystal structures of isolated 20S proteasome complex demonstrate that the two rings of beta subunits form a proteolytic chamber and maintain all their active sites of proteolysis within the chamber.[12] Concomitantly, the rings of alpha subunits form the entrance for substrates entering the proteolytic chamber. In an inactivated 20S proteasome complex, the gate into the internal proteolytic chamber are guarded by the N-terminal tails of specific alpha-subunit. This unique structure design prevents random encounter between proteolytic active sites and protein substrate, which makes protein degradation a well-regulated process.[13][14] 20S proteasome complex, by itself, is usually functionally inactive. The proteolytic capacity of 20S core particle (CP) can be activated when CP associates with one or two regulatory particles (RP) on one or both side of alpha rings. These regulatory particles include 19S proteasome complexes, 11S proteasome complex, etc. Following the CP-RP association, the confirmation of certain alpha subunits will change and consequently cause the opening of substrate entrance gate. Besides RPs, the 20S proteasomes can also be effectively activated by other mild chemical treatments, such as exposure to low levels of sodium dodecylsulfate (SDS) or NP-14.[14][15]

The 20S proteasome subunit beta-2i (systematic nomenclature) is originally expressed as a precursor with 273 amino acids. The fragment of 39 amino acids at peptide N-terminal is essential for proper protein folding and subsequent complex assembly. At the end-stage of complex assembly, the N-terminal fragment of beta2i subunit is cleaved, forming the mature beta2i subunit of 20S complex.[16] During the basal assembly, and proteolytic processing is required to generate a mature subunit. The subunit beta5i only presents in the immunoproteasome and is replaced by subunit beta5(proteasome beta 5 subunit) in constitutive 20S proteasome complex. This protein has an important function in the immune system as part of an immunoproteasome which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation.[6]

Clinical significance

The proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future.

The proteasomes form a pivotal component for the ubiquitin–proteasome system (UPS) [17] and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis.[18] Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases,[19][20] cardiovascular diseases,[21][22][23] inflammatory responses and autoimmune diseases,[24] and systemic DNA damage responses leading to malignancies.[25]

Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease,[26] Parkinson's disease[27] and Pick's disease,[28] Amyotrophic lateral sclerosis (ALS),[28] Huntington's disease,[27] Creutzfeldt–Jakob disease,[29] and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies[30] and several rare forms of neurodegenerative diseases associated with dementia.[31] As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury,[32] ventricular hypertrophy[33] and heart failure.[34] Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.[35] Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel–Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, ABL). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO).[24] Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors.[36] Lastly, autoimmune disease patients with SLE, Sjögren syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.[37]

During the antigen processing for the major histocompatibility complex (MHC) class-I, the proteasome is the major degradation machinery that degrades the antigen and present the resulting peptides to cytotoxic T lymphocytes.[38][39] The immunoproteasome has been considered playing a critical role in improving the quality and quantity of generated class-I ligands.

References

1. GRCh38: Ensembl release 89: ENSG00000205220 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031897 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Larsen F, Solheim J, Kristensen T, Kolstø AB, Prydz H (Oct 1993). "A tight cluster of five unrelated human genes on chromosome 16q22.1". Human Molecular Genetics. 2 (10): 1589–95. doi:10.1093/hmg/2.10.1589. PMID 8268911.
6. Kasthuri SR, Umasuthan N, Whang I, Lim BS, Jung HB, Oh MJ, Jung SJ, Yeo SY, Kim SY, Lee J (Aug 2014). "Molecular characterization and expressional affirmation of the beta proteasome subunit cluster in rock bream immune defense". Molecular Biology Reports. 41 (8): 5413–27. doi:10.1007/s11033-014-3413-1. PMID 24867079.
7. Maldonado M, Kapphahn RJ, Terluk MR, Heuss ND, Yuan C, Gregerson DS, Ferrington DA (2013). "Immunoproteasome deficiency modifies the alternative pathway of NFκB signaling". PLOS ONE. 8 (2): e56187. Bibcode:2013PLoSO...856187M. doi:10.1371/journal.pone.0056187. PMC 3572990. PMID 23457524.
8. "Entrez Gene: PSMB10 proteasome (prosome, macropain) subunit, beta type, 10".
9. Coux O, Tanaka K, Goldberg AL (Nov 1996). "Structure and functions of the 20S and 26S proteasomes". Annual Review of Biochemistry. 65: 801–47. doi:10.1146/annurev.bi.65.070196.004101. PMID 8811196.
10. Basler M, Kirk CJ, Groettrup M (Feb 2013). "The immunoproteasome in antigen processing and other immunological functions". Current Opinion in Immunology. 25 (1): 74–80. doi:10.1016/j.coi.2012.11.004. PMID 23219269.
11. Coux O, Tanaka K, Goldberg AL (1996). "Structure and functions of the 20S and 26S proteasomes". Annual Review of Biochemistry. 65: 801–47. doi:10.1146/annurev.bi.65.070196.004101. PMID 8811196.
12. Tomko RJ, Hochstrasser M (2013). "Molecular architecture and assembly of the eukaryotic proteasome". Annual Review of Biochemistry. 82: 415–45. doi:10.1146/annurev-biochem-060410-150257. PMC 3827779. PMID 23495936.
13. Groll M, Ditzel L, Löwe J, Stock D, Bochtler M, Bartunik HD, Huber R (Apr 1997). "Structure of 20S proteasome from yeast at 2.4 A resolution". Nature. 386 (6624): 463–71. Bibcode:1997Natur.386..463G. doi:10.1038/386463a0. PMID 9087403.
14. Groll M, Bajorek M, Köhler A, Moroder L, Rubin DM, Huber R, Glickman MH, Finley D (Nov 2000). "A gated channel into the proteasome core particle". Nature Structural Biology. 7 (11): 1062–7. doi:10.1038/80992. PMID 11062564.
15. Zong C, Gomes AV, Drews O, Li X, Young GW, Berhane B, Qiao X, French SW, Bardag-Gorce F, Ping P (Aug 2006). "Regulation of murine cardiac 20S proteasomes: role of associating partners". Circulation Research. 99 (4): 372–80. doi:10.1161/01.RES.0000237389.40000.02. PMID 16857963.
16. Yang Y, Früh K, Ahn K, Peterson PA (Nov 1995). "In vivo assembly of the proteasomal complexes, implications for antigen processing". The Journal of Biological Chemistry. 270 (46): 27687–94. doi:10.1074/jbc.270.46.27687. PMID 7499235.
17. Kleiger G, Mayor T (Jun 2014). "Perilous journey: a tour of the ubiquitin–proteasome system". Trends in Cell Biology. 24 (6): 352–9. doi:10.1016/j.tcb.2013.12.003. PMC 4037451. PMID 24457024.
18. Goldberg AL, Stein R, Adams J (Aug 1995). "New insights into proteasome function: from archaebacteria to drug development". Chemistry & Biology. 2 (8): 503–8. doi:10.1016/1074-5521(95)90182-5. PMID 9383453.
19. Sulistio YA, Heese K (Jan 2015). "The Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in Alzheimer's Disease". Molecular Neurobiology. 53 (2): 905–31. doi:10.1007/s12035-014-9063-4. PMID 25561438.
20. Ortega Z, Lucas JJ (2014). "Ubiquitin-proteasome system involvement in Huntington's disease". Frontiers in Molecular Neuroscience. 7: 77. doi:10.3389/fnmol.2014.00077. PMC 4179678. PMID 25324717.
21. Sandri M, Robbins J (Jun 2014). "Proteotoxicity: an underappreciated pathology in cardiac disease". Journal of Molecular and Cellular Cardiology. 71: 3–10. doi:10.1016/j.yjmcc.2013.12.015. PMC 4011959. PMID 24380730.
22. Drews O, Taegtmeyer H (Dec 2014). "Targeting the ubiquitin-proteasome system in heart disease: the basis for new therapeutic strategies". Antioxidants & Redox Signaling. 21 (17): 2322–43. doi:10.1089/ars.2013.5823. PMC 4241867. PMID 25133688.
23. Wang ZV, Hill JA (Feb 2015). "Protein quality control and metabolism: bidirectional control in the heart". Cell Metabolism. 21 (2): 215–26. doi:10.1016/j.cmet.2015.01.016. PMC 4317573. PMID 25651176.
24. Karin M, Delhase M (Feb 2000). "The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling". Seminars in Immunology. 12 (1): 85–98. doi:10.1006/smim.2000.0210. PMID 10723801.
25. Ermolaeva MA, Dakhovnik A, Schumacher B (Jan 2015). "Quality control mechanisms in cellular and systemic DNA damage responses". Ageing Research Reviews. 23 (Pt A): 3–11. doi:10.1016/j.arr.2014.12.009. PMC 4886828. PMID 25560147.
26. Checler F, da Costa CA, Ancolio K, Chevallier N, Lopez-Perez E, Marambaud P (Jul 2000). "Role of the proteasome in Alzheimer's disease". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1502 (1): 133–8. doi:10.1016/s0925-4439(00)00039-9. PMID 10899438.
27. Chung KK, Dawson VL, Dawson TM (Nov 2001). "The role of the ubiquitin-proteasomal pathway in Parkinson's disease and other neurodegenerative disorders". Trends in Neurosciences. 24 (11 Suppl): S7–14. doi:10.1016/s0166-2236(00)01998-6. PMID 11881748.
28. Ikeda K, Akiyama H, Arai T, Ueno H, Tsuchiya K, Kosaka K (Jul 2002). "Morphometrical reappraisal of motor neuron system of Pick's disease and amyotrophic lateral sclerosis with dementia". Acta Neuropathologica. 104 (1): 21–8. doi:10.1007/s00401-001-0513-5. PMID 12070660.
29. Manaka H, Kato T, Kurita K, Katagiri T, Shikama Y, Kujirai K, Kawanami T, Suzuki Y, Nihei K, Sasaki H (May 1992). "Marked increase in cerebrospinal fluid ubiquitin in Creutzfeldt–Jakob disease". Neuroscience Letters. 139 (1): 47–9. doi:10.1016/0304-3940(92)90854-z. PMID 1328965.
30. Mathews KD, Moore SA (Jan 2003). "Limb-girdle muscular dystrophy". Current Neurology and Neuroscience Reports. 3 (1): 78–85. doi:10.1007/s11910-003-0042-9. PMID 12507416.
31. Mayer RJ (Mar 2003). "From neurodegeneration to neurohomeostasis: the role of ubiquitin". Drug News & Perspectives. 16 (2): 103–8. doi:10.1358/dnp.2003.16.2.829327. PMID 12792671.
32. Calise J, Powell SR (Feb 2013). "The ubiquitin proteasome system and myocardial ischemia". American Journal of Physiology. Heart and Circulatory Physiology. 304 (3): H337–49. doi:10.1152/ajpheart.00604.2012. PMC 3774499. PMID 23220331.
33. Predmore JM, Wang P, Davis F, Bartolone S, Westfall MV, Dyke DB, Pagani F, Powell SR, Day SM (Mar 2010). "Ubiquitin proteasome dysfunction in human hypertrophic and dilated cardiomyopathies". Circulation. 121 (8): 997–1004. doi:10.1161/CIRCULATIONAHA.109.904557. PMC 2857348. PMID 20159828.
34. Powell SR (Jul 2006). "The ubiquitin–proteasome system in cardiac physiology and pathology". American Journal of Physiology. Heart and Circulatory Physiology. 291 (1): H1–H19. doi:10.1152/ajpheart.00062.2006. PMID 16501026.
35. Adams J (Apr 2003). "Potential for proteasome inhibition in the treatment of cancer". Drug Discovery Today. 8 (7): 307–15. doi:10.1016/s1359-6446(03)02647-3. PMID 12654543.
36. Ben-Neriah Y (Jan 2002). "Regulatory functions of ubiquitination in the immune system". Nature Immunology. 3 (1): 20–6. doi:10.1038/ni0102-20. PMID 11753406.
37. Egerer K, Kuckelkorn U, Rudolph PE, Rückert JC, Dörner T, Burmester GR, Kloetzel PM, Feist E (Oct 2002). "Circulating proteasomes are markers of cell damage and immunologic activity in autoimmune diseases". The Journal of Rheumatology. 29 (10): 2045–52. PMID 12375310.
38. Basler M, Lauer C, Beck U, Groettrup M (Nov 2009). "The proteasome inhibitor bortezomib enhances the susceptibility to viral infection". Journal of Immunology. 183 (10): 6145–50. doi:10.4049/jimmunol.0901596. PMID 19841190.
39. Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D, Goldberg AL (Sep 1994). "Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules". Cell. 78 (5): 761–71. doi:10.1016/s0092-8674(94)90462-6. PMID 8087844.

Further reading

• Coux O, Tanaka K, Goldberg AL (1996). "Structure and functions of the 20S and 26S proteasomes". Annual Review of Biochemistry. 65: 801–47. doi:10.1146/annurev.bi.65.070196.004101. PMID 8811196.
• Goff SP (Aug 2003). "Death by deamination: a novel host restriction system for HIV-1". Cell. 114 (3): 281–3. doi:10.1016/S0092-8674(03)00602-0. PMID 12914693.
• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Hisamatsu H, Shimbara N, Saito Y, Kristensen P, Hendil KB, Fujiwara T, Takahashi E, Tanahashi N, Tamura T, Ichihara A, Tanaka K (Apr 1996). "Newly identified pair of proteasomal subunits regulated reciprocally by interferon gamma". The Journal of Experimental Medicine. 183 (4): 1807–16. doi:10.1084/jem.183.4.1807. PMC 2192534. PMID 8666937.
• Seeger M, Ferrell K, Frank R, Dubiel W (Mar 1997). "HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation". The Journal of Biological Chemistry. 272 (13): 8145–8. doi:10.1074/jbc.272.13.8145. PMID 9079628.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Foss GS, Larsen F, Solheim J, Prydz H (Mar 1998). "Constitutive and interferon-gamma-induced expression of the human proteasome subunit multicatalytic endopeptidase complex-like 1". Biochimica et Biophysica Acta. 1402 (1): 17–28. doi:10.1016/S0167-4889(97)00152-3. PMID 9551082.
• Madani N, Kabat D (Dec 1998). "An endogenous inhibitor of human immunodeficiency virus in human lymphocytes is overcome by the viral Vif protein". Journal of Virology. 72 (12): 10251–5. doi:10.1128/JVI.72.12.10251-10255.1998. PMC 110608. PMID 9811770.
• Simon JH, Gaddis NC, Fouchier RA, Malim MH (Dec 1998). "Evidence for a newly discovered cellular anti-HIV-1 phenotype". Nature Medicine. 4 (12): 1397–400. doi:10.1038/3987. PMID 9846577.
• Schmidt M, Zantopf D, Kraft R, Kostka S, Preissner R, Kloetzel PM (Apr 1999). "Sequence information within proteasomal prosequences mediates efficient integration of beta-subunits into the 20 S proteasome complex". Journal of Molecular Biology. 288 (1): 117–28. doi:10.1006/jmbi.1999.2660. PMID 10329130.
• Elenich LA, Nandi D, Kent AE, McCluskey TS, Cruz M, Iyer MN, Woodward EC, Conn CW, Ochoa AL, Ginsburg DB, Monaco JJ (Sep 1999). "The complete primary structure of mouse 20S proteasomes". Immunogenetics. 49 (10): 835–42. doi:10.1007/s002510050562. PMID 10436176.
• Mulder LC, Muesing MA (Sep 2000). "Degradation of HIV-1 integrase by the N-end rule pathway". The Journal of Biological Chemistry. 275 (38): 29749–53. doi:10.1074/jbc.M004670200. PMID 10893419.
• Sheehy AM, Gaddis NC, Choi JD, Malim MH (Aug 2002). "Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein". Nature. 418 (6898): 646–50. Bibcode:2002Natur.418..646S. doi:10.1038/nature00939. PMID 12167863.
• Chagnon P, Michaud J, Mitchell G, Mercier J, Marion JF, Drouin E, Rasquin-Weber A, Hudson TJ, Richter A (Dec 2002). "A missense mutation (R565W) in cirhin (FLJ14728) in North American Indian childhood cirrhosis". American Journal of Human Genetics. 71 (6): 1443–9. doi:10.1086/344580. PMC 378590. PMID 12417987.
• Huang X, Seifert U, Salzmann U, Henklein P, Preissner R, Henke W, Sijts AJ, Kloetzel PM, Dubiel W (Nov 2002). "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. doi:10.1016/S0022-2836(02)00998-1. PMID 12419264.
• Miyagi T, Tatsumi T, Takehara T, Kanto T, Kuzushita N, Sugimoto Y, Jinushi M, Kasahara A, Sasaki Y, Hori M, Hayashi N (Jan 2003). "Impaired expression of proteasome subunits and human leukocyte antigens class I in human colon cancer cells". Journal of Gastroenterology and Hepatology. 18 (1): 32–40. doi:10.1046/j.1440-1746.2003.02921.x. PMID 12519221.
• Gaddis NC, Chertova E, Sheehy AM, Henderson LE, Malim MH (May 2003). "Comprehensive investigation of the molecular defect in vif-deficient human immunodeficiency virus type 1 virions". Journal of Virology. 77 (10): 5810–20. doi:10.1128/JVI.77.10.5810-5820.2003. PMC 154025. PMID 12719574.