PSMB7

Proteasome subunit beta type-7 as known as 20S proteasome subunit beta-2 is a protein that in humans is encoded by the PSMB7 gene.[4][5]

PSMB7
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4R3O, 4R67, 5A0Q
Identifiers
Aliases	PSMB7, proteasome subunit beta 7, Z, proteasome 20S subunit beta 7
External IDs	OMIM: 604030 MGI: 107637 HomoloGene: 2093 GeneCards: PSMB7
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q33.3 Start 124,353,465 bp[1] End 124,415,444 bp[1]
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 • nucleoplasm • proteasome complex • extracellular exosome • cell nucleus • proteasome core complex • extracellular region • cytoplasm • cytosol • secretory granule lumen • ficolin-1-rich granule lumen • proteasome core complex, beta-subunit complex Biological process • regulation of cellular amino acid metabolic process • antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent • regulation of mRNA stability • positive regulation of protein targeting to mitochondrion • positive regulation of canonical Wnt signaling pathway • protein polyubiquitination • stimulatory C-type lectin receptor signaling pathway • tumor necrosis factor-mediated signaling pathway • MAPK cascade • proteolysis • Fc-epsilon receptor signaling pathway • NIK/NF-kappaB signaling • anaphase-promoting complex-dependent catabolic process • proteolysis involved in cellular protein catabolic process • T cell receptor signaling pathway • negative regulation of canonical Wnt signaling pathway • Wnt signaling pathway, planar cell polarity pathway • proteasome-mediated ubiquitin-dependent protein catabolic process • GO:0022415 viral process • negative regulation of G2/M transition of mitotic cell cycle • protein deubiquitination • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process • neutrophil degranulation • transmembrane transport • regulation of transcription from RNA polymerase II promoter in response to hypoxia • post-translational modification • regulation of hematopoietic stem cell differentiation • proteasomal protein catabolic process • proteasomal ubiquitin-independent protein catabolic process • interleukin-1-mediated signaling pathway • regulation of mitotic cell cycle phase transition Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5695	19177
Ensembl	ENSG00000136930	n/a
UniProt	Q99436 Q5TBG5	P70195
RefSeq (mRNA)	NM_002799	NM_011187
RefSeq (protein)	NP_002790	NP_035317
Location (UCSC)	Chr 9: 124.35 – 124.42 Mb	n/a
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

This protein 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 type-5, 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.[4] The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides.

Structure

Gene

The human PSMB7 gene has 8 exons and locates at chromosome band 9q34.11-q34.12.

Protein

The gene PSMB7 encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit in the proteasome. Expression of this catalytic subunit (beta 2, according to systematic nomenclature) is downregulated by gamma interferon due to an alternatively elevated expression of inducible subunit beta2i, which leads to augmented incorporation of beta2i instead of beta2 into the final assembled 20S complex.[5] The human protein proteasome subunit beta type-7 is 25 kDa in size and composed of 234 amino acids. The calculated theoretical pI of this protein is 5.61.

Complex assembly

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.[6][7]

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.[7] 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.[8][9] 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.[9][10]

The 20S proteasome subunit beta-2 (systematic nomenclature) is originally expressed as a precursor with 277 amino acids. The fragment of 43 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 beta5 subunit is cleaved, forming the mature beta2 subunit of 20S complex.[11] During the basal assembly, and proteolytic processing is required to generate a mature subunit. This subunit is not present in the immunoproteasome and is replaced by catalytic subunit 2i (proteasome beta 10 subunit).

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) [12] 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.[13] 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,[14][15] cardiovascular diseases,[16][17][18] inflammatory responses and autoimmune diseases,[19] and systemic DNA damage responses leading to malignancies.[20]

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,[21] Parkinson's disease[22] and Pick's disease,[23] Amyotrophic lateral sclerosis (ALS),[23] Huntington's disease,[22] Creutzfeldt–Jakob disease,[24] and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies[25] and several rare forms of neurodegenerative diseases associated with dementia.[26] As part of the ubiquitin–proteasome system (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury,[27] ventricular hypertrophy[28] and heart failure.[29] 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.[30] 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).[19] 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.[31] Lastly, autoimmune disease patients with SLE, Sjögren syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.[32]

The PSMB7 protein has a variety of clinically relevant constituents. For instance, in breast cancer cells, a high expression level of the PSMB7 protein suggests a shorter survival than in cells with a lower expression level.[33] This interesting finding indicates that the PSMB7 protein may be used as a clinical prognostic biomarker in breast cancer.[33] The same study also suggested that the PSMB7 protein is involved in anthracycline resistance, which is an antibiotic derived from streptomyces bacteria and used as an anticancer chemotherapy for leukemias, lymphomas, breast cancer, uterine, ovarian and lung cancers.[34] Furthermore, the PSMB7 protein may also be involved in the resistance to 5-fluoro uracil (5-FU) therapy. Targeting the PSMB7 gene, to down-regulate PSMB7 protein, may overcome resistance to 5-FU and thus a possible new approach to treat hepatocellular carcinoma with this chemotherapeutic drug.[35] High PSMB7 expression is an unfavourable prognostic marker in breast cancer.[33] In this, survival of resistant breast cancer cell lines decreased after doxorubicin or paclitaxel treatment when PSMB7 was knocked down by RNA interference. These results were validated in 1592 microarray samples: patients with high PSMB7 expression had a significantly shorter survival than patients with low expression. Knockdown of the PSMB7 gene may also induce autophagy in cardiomyocytes.[36]

References

1. GRCh38: Ensembl release 89: ENSG00000136930 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. 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.
5. "Entrez Gene: PSMB7 proteasome (prosome, macropain) subunit, beta type, 7".
6. 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.
7. 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.
8. Groll M, Ditzel L, Löwe J, Stock D, Bochtler M, Bartunik HD, Huber R (April 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.
9. Groll M, Bajorek M, Köhler A, Moroder L, Rubin DM, Huber R, Glickman MH, Finley D (November 2000). "A gated channel into the proteasome core particle". Nature Structural Biology. 7 (11): 1062–7. doi:10.1038/80992. PMID 11062564.
10. Zong C, Gomes AV, Drews O, Li X, Young GW, Berhane B, Qiao X, French SW, Bardag-Gorce F, Ping P (August 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.
11. Yang Y, Früh K, Ahn K, Peterson PA (November 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.
12. Kleiger G, Mayor T (June 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.
13. Goldberg AL, Stein R, Adams J (August 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.
14. Sulistio YA, Heese K (March 2016). "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.
15. 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.
16. Sandri M, Robbins J (June 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.
17. Drews O, Taegtmeyer H (December 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.
18. Wang ZV, Hill JA (February 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.
19. Karin M, Delhase M (February 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.
20. Ermolaeva MA, Dakhovnik A, Schumacher B (September 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.
21. Checler F, da Costa CA, Ancolio K, Chevallier N, Lopez-Perez E, Marambaud P (July 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.
22. Chung KK, Dawson VL, Dawson TM (November 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.
23. Ikeda K, Akiyama H, Arai T, Ueno H, Tsuchiya K, Kosaka K (July 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.
24. 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.
25. Mathews KD, Moore SA (January 2003). "Limb-girdle muscular dystrophy". Current Neurology and Neuroscience Reports. 3 (1): 78–85. doi:10.1007/s11910-003-0042-9. PMID 12507416.
26. Mayer RJ (March 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.
27. Calise J, Powell SR (February 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.
28. Predmore JM, Wang P, Davis F, Bartolone S, Westfall MV, Dyke DB, Pagani F, Powell SR, Day SM (March 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.
29. Powell SR (July 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.
30. Adams J (April 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.
31. Ben-Neriah Y (January 2002). "Regulatory functions of ubiquitination in the immune system". Nature Immunology. 3 (1): 20–6. doi:10.1038/ni0102-20. PMID 11753406.
32. Egerer K, Kuckelkorn U, Rudolph PE, Rückert JC, Dörner T, Burmester GR, Kloetzel PM, Feist E (October 2002). "Circulating proteasomes are markers of cell damage and immunologic activity in autoimmune diseases". The Journal of Rheumatology. 29 (10): 2045–52. PMID 12375310.
33. Munkácsy G, Abdul-Ghani R, Mihály Z, Tegze B, Tchernitsa O, Surowiak P, Schäfer R, Györffy B (January 2010). "PSMB7 is associated with anthracycline resistance and is a prognostic biomarker in breast cancer". British Journal of Cancer. 102 (2): 361–8. doi:10.1038/sj.bjc.6605478. PMC 2816652. PMID 20010949.
34. Weiss RB (December 1992). "The anthracyclines: will we ever find a better doxorubicin?". Seminars in Oncology. 19 (6): 670–86. PMID 1462166.
35. Tan Y, Qin S, Hou X, Qian X, Xia J, Li Y, Wang R, Chen C, Yang Q, Miele L, Wu Q, Wang Z (2014). "Proteomic-based analysis for identification of proteins involved in 5-fluorouracil resistance in hepatocellular carcinoma". Current Pharmaceutical Design. 20 (1): 81–7. doi:10.2174/138161282001140113125143. PMID 23530500.
36. Kyrychenko VO, Nagibin VS, Tumanovska LV, Pashevin DO, Gurianova VL, Moibenko AA, Dosenko VE, Klionsky DJ (2014). "Knockdown of PSMB7 induces autophagy in cardiomyocyte cultures: possible role in endoplasmic reticulum stress". Pathobiology. 81 (1): 8–14. doi:10.1159/000350704. PMID 23969338.

Further reading

• Rivett AJ, Bose S, Brooks P, Broadfoot KI (2001). "Regulation of proteasome complexes by gamma-interferon and phosphorylation". Biochimie. 83 (3–4): 363–6. doi:10.1016/S0300-9084(01)01249-4. PMID 11295498.
• Goff SP (August 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.
• Kristensen P, Johnsen AH, Uerkvitz W, Tanaka K, Hendil KB (December 1994). "Human proteasome subunits from 2-dimensional gels identified by partial sequencing". Biochemical and Biophysical Research Communications. 205 (3): 1785–9. doi:10.1006/bbrc.1994.2876. PMID 7811265.
• Maruyama K, Sugano S (January 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 (April 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 (March 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 (October 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.
• Madani N, Kabat D (December 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 (December 1998). "Evidence for a newly discovered cellular anti-HIV-1 phenotype". Nature Medicine. 4 (12): 1397–400. doi:10.1038/3987. PMID 9846577.
• O'Hare T, Wiens GD, Whitcomb EA, Enns CA, Rittenberg MB (July 1999). "Cutting edge: proteasome involvement in the degradation of unassembled Ig light chains". Journal of Immunology. 163 (1): 11–4. PMID 10384092.
• Elenich LA, Nandi D, Kent AE, McCluskey TS, Cruz M, Iyer MN, Woodward EC, Conn CW, Ochoa AL, Ginsburg DB, Monaco JJ (September 1999). "The complete primary structure of mouse 20S proteasomes". Immunogenetics. 49 (10): 835–42. doi:10.1007/s002510050562. PMID 10436176.
• Mulder LC, Muesing MA (September 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.
• Feng Y, Longo DL, Ferris DK (January 2001). "Polo-like kinase interacts with proteasomes and regulates their activity". Cell Growth & Differentiation. 12 (1): 29–37. PMID 11205743.
• Sheehy AM, Gaddis NC, Choi JD, Malim MH (August 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.
• Huang X, Seifert U, Salzmann U, Henklein P, Preissner R, Henke W, Sijts AJ, Kloetzel PM, Dubiel W (November 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.
• 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.