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Gene Review

PSMD2  -  proteasome (prosome, macropain) 26S...

Homo sapiens

Synonyms: 26S proteasome non-ATPase regulatory subunit 2, 26S proteasome regulatory subunit RPN1, 26S proteasome regulatory subunit S2, 26S proteasome subunit p97, MGC14274, ...
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Disease relevance of PSMD2

  • TEF-1 binding in vivo was necessary for HPV-16 P97 promoter activity [1].
  • C-Met, beta1 --> 4GalNAc-T and P97 tumor mRNA markers were expressed in 31 (78%), 21 (53%) and 25 (63%) of 40 SNs without metastases, respectively [2].
  • E6*I cDNA was able to trans-activate the autologous P97 promoter and the heterologous adenovirus E2 promoter [3].
  • To clarify the heavy chain structure required for the regulation, smooth muscle myosin containing 7 different lengths of the S-2 portion were expressed in Sf9 insect cells using Baculovirus expression system [4].
  • In HPV-16 DNA from cervical carcinomas, mutations of YY1-binding sites have been identified that increase P97 activity 3-6-fold [5].

High impact information on PSMD2

  • Mutations were also generated in the E2-binding sites located upstream of the P97 promoter, which directs synthesis of the viral E6 and E7 transforming genes [6].
  • The components of rod, light meromyosin (LMM) and subfragment-2 (S-2), were prepared by proteolysis of myosin and rod, respectively, using trypsin treated with tosylphenylalanine chloromethyl ketone [7].
  • Gel shift experiments showed a specific binding of recombinant c-Myb protein on the HPV-16 P97 enhancer [8].
  • The 97-kDa TNFR-associated protein, TRAP2, shows sequence identity with internal amino acid sequences from subunit 2 of the 26S protease [9].
  • TRAP2 antiserum interacted with the 97-kDa protein in HeLa cell lysates and cytosol, the latter observation showing that TRAP2 resides in the same cellular compartment as TNFR-1IC [9].

Biological context of PSMD2

  • The hrd2-1 mutant had numerous pleiotropic phenotypes expected for cells with a compromised proteasome, and these phenotypes were complemented by the human TRAP-2/p97 coding region [10].
  • The Sp1 binding site is needed to mediate activation of P97 by the remote epithelial-specific enhancer, and the two E2 binding sites contribute to a negative feedback-loop of viral gene expression [11].
  • We show here, that in CaSki cells, which contain HPV-16 genomes, P97 is also inducible by phorbol esters [12].
  • An HPV31b early promoter, P97, and a differentiation-induced promoter, P742, have been characterized by using this system [13].
  • These RNAs initiated at a promoter, P97, in the upstream regulatory region of the virus [14].

Anatomical context of PSMD2

  • After in vitro transcription/translation and 35S labeling, TRAP2 was precipitated from a cellfree system by GST-TNFR-1IC, showing that TNFR-1IC and TRAP2 interact directly [9].
  • Moreover, P97 transcytosis across bovine brain capillary endothelial cell (BBCEC) monolayers is at least 14-fold higher than that of holo-transferrin, with no apparent intra-endothelial degradation [15].
  • High transcytosis of melanotransferrin (P97) across the blood-brain barrier [15].
  • Human papillomavirus type 16 immortalized cervical keratinocytes contain transcripts encoding E6, E7, and E2 initiated at the P97 promoter and express high levels of E7 [16].
  • A monoclonal antibody against subfragment 2 (S-2) of smooth muscle myosin, designated MM-9, was generated and characterized [17].

Associations of PSMD2 with chemical compounds

  • This region composed of 520 amino-acid residues which span the connecting segment between subfragment-1 (S-1) and S-2 to the NH2-terminal portion of light meromyosin (LMM) [18].
  • The complete primary structure of the subfragment-2 (S-2) from adult chicken cardiac ventricular muscle myosin has been determined by analysis of peptides derived from digests of S-2 with cyanogen bromide, lysyl endopeptidase, arginyl endopeptidase, and from hydrolysates of CNBr fragments with formic acid [18].
  • The activity of P97 is regulated by a cell-type-specific enhancer, as well as by glucocorticoids and progesterone [12].
  • Firefly luciferase activity expressed under the control of the HPV16 upstream regulatory region and P97 promoter increased by about fourfold following dexamethasone treatment of HeLa, but only twofold in HKc/HPV16, and less than twofold in SiHa [19].
  • Interestingly, only simultaneous, but not individual substitution of the highly conserved D90, F94, P97 and G99 residues with alanine interfered with PEN-2 function [20].

Other interactions of PSMD2


Analytical, diagnostic and therapeutic context of PSMD2

  • The unfolding temperature for the 40 kDa S-2 was around 52 degrees C as studied by circular dichroism measurement [22].
  • We demonstrate here that recombinant human melanotransferrin (P97) is highly accumulated into the mouse brain following intravenous injection and in situ brain perfusion [15].
  • Six consecutive 12-microm frozen sections of each SN were obtained for the RT-PCR assay to determine expression of mRNA tumor markers C-Met, beta1 --> 4GalNAc-T and P97 [2].
  • Sequence analysis of the long control region of human papillomavirus type 16 variants and functional consequences for P97 promoter activity [23].
  • Furthermore, P97 content in tumor and tissues of IFN-treated mice bearing melanoma xenografts was significantly higher than in mice without tumors [24].


  1. Transcriptional enhancer factor (TEF)-1 and its cell-specific co-activator activate human papillomavirus-16 E6 and E7 oncogene transcription in keratinocytes and cervical carcinoma cells. Ishiji, T., Lace, M.J., Parkkinen, S., Anderson, R.D., Haugen, T.H., Cripe, T.P., Xiao, J.H., Davidson, I., Chambon, P., Turek, L.P. EMBO J. (1992) [Pubmed]
  2. Detection of metastases in sentinel lymph nodes of breast cancer patients by multiple-marker RT-PCR. Bostick, P.J., Huynh, K.T., Sarantou, T., Turner, R.R., Qi, K., Giuliano, A.E., Hoon, D.S. Int. J. Cancer (1998) [Pubmed]
  3. Transcription-modulatory activity of full-length E6 and E6*I proteins of human papillomavirus type 16. Shirasawa, H., Jin, M.H., Shimizu, K., Akutsu, N., Shino, Y., Simizu, B. Virology (1994) [Pubmed]
  4. Requirement of the two-headed structure for the phosphorylation dependent regulation of smooth muscle myosin. Matsu-ura, M., Ikebe, M. FEBS Lett. (1995) [Pubmed]
  5. Overlapping YY1- and aberrant SP1-binding sites proximal to the early promoter of human papillomavirus type 16. Dong, X.P., Pfister, H. J. Gen. Virol. (1999) [Pubmed]
  6. Disruption of either the E1 or the E2 regulatory gene of human papillomavirus type 16 increases viral immortalization capacity. Romanczuk, H., Howley, P.M. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  7. Flexibility of myosin rod, light meromyosin, and myosin subfragment-2 in solution. Highsmith, S., Kretzschmar, K.M., O'Konski, C.T., Morales, M.F. Proc. Natl. Acad. Sci. U.S.A. (1977) [Pubmed]
  8. Human c-myb is expressed in cervical carcinomas and transactivates the HPV-16 promoter. Nürnberg, W., Artuc, M., Nawrath, M., Lovric, J., Stüting, S., Moelling, K., Czarnetzki, B.M., Schadendorf, D. Cancer Res. (1995) [Pubmed]
  9. Two-hybrid cloning of a gene encoding TNF receptor-associated protein 2, a protein that interacts with the intracellular domain of the type 1 TNF receptor: identity with subunit 2 of the 26S protease. Dunbar, J.D., Song, H.Y., Guo, D., Wu, L.W., Donner, D.B. J. Immunol. (1997) [Pubmed]
  10. Role of 26S proteasome and HRD genes in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein. Hampton, R.Y., Gardner, R.G., Rine, J. Mol. Biol. Cell (1996) [Pubmed]
  11. During negative regulation of the human papillomavirus-16 E6 promoter, the viral E2 protein can displace Sp1 from a proximal promoter element. Tan, S.H., Gloss, B., Bernard, H.U. Nucleic Acids Res. (1992) [Pubmed]
  12. Transcription of the transforming genes of the oncogenic human papillomavirus-16 is stimulated by tumor promotors through AP1 binding sites. Chan, W.K., Chong, T., Bernard, H.U., Klock, G. Nucleic Acids Res. (1990) [Pubmed]
  13. Characterization of late gene transcripts expressed during vegetative replication of human papillomavirus type 31b. Ozbun, M.A., Meyers, C. J. Virol. (1997) [Pubmed]
  14. Differentiation-induced and constitutive transcription of human papillomavirus type 31b in cell lines containing viral episomes. Hummel, M., Hudson, J.B., Laimins, L.A. J. Virol. (1992) [Pubmed]
  15. High transcytosis of melanotransferrin (P97) across the blood-brain barrier. Demeule, M., Poirier, J., Jodoin, J., Bertrand, Y., Desrosiers, R.R., Dagenais, C., Nguyen, T., Lanthier, J., Gabathuler, R., Kennard, M., Jefferies, W.A., Karkan, D., Tsai, S., Fenart, L., Cecchelli, R., Béliveau, R. J. Neurochem. (2002) [Pubmed]
  16. Human papillomavirus type 16 immortalized cervical keratinocytes contain transcripts encoding E6, E7, and E2 initiated at the P97 promoter and express high levels of E7. Nasseri, M., Gage, J.R., Lorincz, A., Wettstein, F.O. Virology (1991) [Pubmed]
  17. Alteration of the enzymatic properties of smooth muscle myosin by a monoclonal antibody against subfragment 2. Higashihara, M., Ikebe, M. FEBS Lett. (1990) [Pubmed]
  18. Primary structure of subfragment-2 from adult chicken cardiac ventricular muscle myosin. Watanabe, B. Biol. Chem. Hoppe-Seyler (1993) [Pubmed]
  19. Glucocorticoids stimulate growth of human papillomavirus type 16 (HPV16)-immortalized human keratinocytes and support HPV16-mediated immortalization without affecting the levels of HPV16 E6/E7 mRNA. Khan, M.A., Canhoto, A.J., Housley, P.R., Creek, K.E., Pirisi, L. Exp. Cell Res. (1997) [Pubmed]
  20. Length and overall sequence of the PEN-2 C-terminal domain determines its function in the stabilization of presenilin fragments. Prokop, S., Haass, C., Steiner, H. J. Neurochem. (2005) [Pubmed]
  21. Mapping of the genes for human endoplasmic reticular heat shock protein gp96/grp94. Maki, R.G., Eddy, R.L., Byers, M., Shows, T.B., Srivastava, P.K. Somat. Cell Mol. Genet. (1993) [Pubmed]
  22. Uniquely stable 40 kDa subfragment-2 in carp myosin. Takahashi, T.T., Takahashi, M., Konno, K. J. Agric. Food Chem. (2005) [Pubmed]
  23. Sequence analysis of the long control region of human papillomavirus type 16 variants and functional consequences for P97 promoter activity. Kämmer, C., Warthorst, U., Torrez-Martinez, N., Wheeler, C.M., Pfister, H. J. Gen. Virol. (2000) [Pubmed]
  24. Recombinant alpha-interferon enhances tumor targeting of an antimelanoma monoclonal antibody in vivo. Murray, J.L., Zukiwski, A.A., Mujoo, K., Rosenblum, M.G. Journal of biological response modifiers. (1990) [Pubmed]
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