Disease relevance of TPP2

• The oligopeptidase tripeptidyl-peptidase II (TPP II) is up-regulated Burkitt's lymphoma (BL) cells that overexpress the c-myc proto-oncogene and is required for their growth and survival [1].
• In addition, extracts of Escherichia coli showed no TPP II activity under the conditions of the standard assay, although polypeptides of Mr 135,000 and 40,000 were revealed on immunoblot analysis of this species [2].
• In the present study, we have examined the activities and levels of the proteasome and TPPII complex in Raji and in Akata cells after induction of EBV lytic cycle [3].
• Our results suggest that a giant serine protease, different from tripeptidyl peptidase II, is involved in the in vitro degradation of HIV-1 RT [4].

High impact information on TPP2

• A major role for TPPII in trimming proteasomal degradation products for MHC class I antigen presentation [5].
• Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII [6].
• The present report presents evidence that the amino acid sequence around the serine of the active site of human tripeptidyl peptidase II is of the subtilisin type [7].
• Active site of tripeptidyl peptidase II from human erythrocytes is of the subtilisin type [7].
• These data demonstrate that human tripeptidyl peptidase II represents a potentially distinct class of human peptidases and raise the question of an evolutionary relationship between the active site of a mammalian peptidase and that of the subtilisin family of serine peptidases [7].

Biological context of TPP2

• We have assigned the human tripeptidyl peptidase II (TPP2) gene to chromosome region 13q32-q33 using two different methods [8].
• The TPP2 sequences were found to segregate with the human chromosome 13 [8].
• The gene encoding human TPP II (TPP2) is 82 kb and consists of 30 exons [9].
• However, antisera to TPP2 fusion protein was specific for the type 2A catalytic subunit and recognized a polypeptide of 35 kDa in a Western blot of crude trypanosomal lysate [10].
• Using proteomics, we identified two cytosolic peptidases, tripeptidyl peptidase II and puromycin-sensitive aminopeptidase, that trimmed the N-terminal extensions of the precursors produced by the proteasome, and led to a transient enrichment of the final antigenic peptide [11].

Anatomical context of TPP2

• First, a full-length TPP2 cDNA was used as a probe on Southern blots of DNA from a panel of human/rodent somatic cell hybrids [8].
• Although we observed some proteolytic activity in fractions enriched in endoplasmic reticulum, it could not compensate for the loss of tripeptidyl peptidase II/puromycin-sensitive aminopeptidase activities [11].
• Mitotic infidelity and centrosome duplication errors in cells overexpressing tripeptidyl-peptidase II [1].
• Similar mitotic aberrations were also observed in a panel of BL lines and were suppressed, in parallel with TPP II down-regulation, upon reversion of BL-like characteristics in EBV-immortalized B lymphocytes carrying a tetracycline-regulated c-myc [1].
• Axonal transports of tripeptidyl peptidase II in rat sciatic nerves [12].

Associations of TPP2 with chemical compounds

• When native TPP II was dissociated into smaller units through dialysis against a dilute Tris buffer, it could be digested by chymotrypsin into three stable fragments of 70 kDa, 42 kDa and 20 kDa [13].
• Antibodies against a 65 kDa cell-binding fragment of fibronectin specifically reacted with TPP II, whereas antibodies against the collagen-binding domain, the main heparin-binding domain or the N-terminal fibrin-binding domain did not react [13].
• There is an in-frame methionine at position 8, which probably represents the starting point of translation, indicating that the complete coding sequence for TPP II now has been determined [14].
• Furthermore, we show that proteasomes are unlikely to generate MHC class I ligands with a C-terminal lysine residue, suggesting processing of these ligands by a different protease that may be tripeptidyl-peptidase II (TPPII) [15].
• Use of a dehydroalanine-containing peptide as an efficient inhibitor of tripeptidyl peptidase II [16].

Physical interactions of TPP2

• Moreover, the affinity-purified antibodies against TPP II reacted with a 105 kDa cell-binding fragment of fibronectin but not with the fibrin-binding domain or the collagen-binding domain [13].

Regulatory relationships of TPP2

• Furthermore, antibodies against human fibronectin cross-reacted with TPP II [13].

Other interactions of TPP2

• Levels of mRNAs for CCK and TPPII show a positive correlation in postmortem human cerebral cortex Brodmann area (BA) 10 [17].
• These results suggest that GAPDH modified by HNE and HHE is degraded by a giant serine protease, releasing the 23-kDa fragment, not by proteasome or TPP II [18].
• At the cell surface, dipeptidyl peptidase IV and tripeptidyl peptidase II (TPPII) activities were also detected, and their activities decreased during time course of batch cultures [19].
• Moreover, AAF-cmk, claimed to be a specific TPP II inhibitor, also inhibits the chymotrypsin-like activity of the proteasome [20].
• Identification of the catalytic triad in tripeptidyl-peptidase II through site-directed mutagenesis [21].

Analytical, diagnostic and therapeutic context of TPP2

• Southern and Northern blot analyses are consistent with TPP2 being encoded by a single copy gene from which is derived a mRNA of 2.5 kb [10].
• Localization of the human tripeptidyl peptidase II gene (TPP2) to 13q32-q33 by nonradioactive in situ hybridization and somatic cell hybrids [8].
• Supramolecular structure of tripeptidyl peptidase II from human erythrocytes as studied by electron microscopy, and its correlation to enzyme activity [22].
• Axonal transport of tripeptidyl peptidase II, a putative cholecystokinin inactivating serine peptidase, was examined in the proximal, middle, and distal segments of rat sciatic nerves using a double ligation technique [12].
• Mutant and wild-type TPP II subunits co-eluted from a gel filtration column, suggesting that the subunits associate and that the native subunit conformation was retained in the mutants [21].

References