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

• Only one of the genes, designated TRA1 (human chromosome 12) is a coding gene; the other genes (TRA1P1 and TRAP2) appear to be independently derived, processed pseudogenes [21].

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].

References