Disease relevance of TMPRSS13

• High levels of MSP were present within infiltrating mononuclear cells, including macrophages and T cells, which characteristically fill sites of demyelination, both in multiple sclerosis lesions and in animal models of this disease [1].
• However, promoter methylation of SFRP1 was frequently observed in both primary breast cancer (61%, n=130) and cell lines analysed by methylation-specific polymerase chain reaction (MSP) [2].
• Overexpression of the matrix serine protease (MSP) trypsin has been implicated in tumour growth, invasion, and metastasis [3].
• When Hpall- and Mspl- digested DNA was probed with BamHI C, E, H and W fragments, the CLL lines showed a mixture of methylated and unmethylated restriction fragments as in certain EBV-carrying Burkitt lymphoma (BL) lines [4].
• To further characterize the activity and substrate specificity of this newly identified enzyme, we have heterologously expressed MSP in a baculovirus/insect cell line system [5].

Psychiatry related information on TMPRSS13

• To clarify individual differences in susceptibility to gallbladder carcinogenesis, we investigated the frequency of the Mspl and Ile-Val polymorphisms of the CYP1A1 gene, in 52 patients with gallbladder cancer (32 females, 20 males) and 104 healthy controls (64 females, 40 males) [6].

High impact information on TMPRSS13

• In the adult rat lumbosacral spinal cord, in situ localization of MSP mRNA demonstrated 2-fold higher levels in the white, as compared with the gray, matter [7].
• A full-length cDNA clone of a previously unidentified serine protease, myelencephalon-specific protease (MSP), has been isolated by using a PCR cloning strategy and has been shown to be expressed in a nervous system and spinal cord-specific pattern [7].
• Sequence analysis demonstrated that MSP is most similar in sequence to neuropsin, trypsin, and tissue kallikrein and is predicted to have trypsin-like substrate specificity [7].
• MSP mRNA expression was shown to increase 3-fold in the white matter and 1.5-fold in the gray laminae at 72 hr after intraperitoneal injection of the AMPA/kainate glutamate receptor-specific agonist, kainic acid (KA) [7].
• Together, these observations indicate that MSP is in a position to play a fundamental role in normal homeostasis and in the response of the spinal cord to injury [7].

Chemical compound and disease context of TMPRSS13

• MSP may be regulated in part by autolysis, since the active protein is readily inactivated through autolysis at specific internal arginine positions [5].
• RESULTS: The extensive methylation within p16 INK4a 5' CpG island was not detected either in 13 primary cervical carcinomas or in 5 cancer cell lines by bisulfite-modified DNA sequencing (including those that were positive by MSP in our hands) [8].

Biological context of TMPRSS13

• Transfection of oligodendrocyte progenitors with an MSP-green fluorescent protein construct produced similar changes in oligodendrocyte process number [1].
• RESULTS: QM-MSP findings on a panel of nine genes were correlated to duct histology and ductal lavage cytology [9].
• We have identified two novel single nucleotide polymorphisms in the 5' region of the human IL-1RI gene: (1) A-->G at position 52 in intron 1B (GenBank accession number AF146426), which creates an Mspl restriction endonuclease site [10].
• We found that the intercoding region between MSPL-coding regions, when cloned downstream of the beta-galactosidase reporter gene (beta-GAL), caused beta-GAL mRNA to increase 8- to 10-fold after inhibiting protein synthesis with cycloheximide [11].
• Major surface protease (MSP) facilitates Leishmania promastigote evasion of complement-mediated lysis in the mammalian host and enhances host macrophage phagocytosis of the promastigotes [12].

Anatomical context of TMPRSS13

• MSP mRNA remained elevated in the ventral gray matter, including expression associated with the motor neurons of lamina IX, at 7 d after the initial excitotoxic insult [7].
• Importantly, r-MSP did not affect oligodendrocyte survival or differentiation towards the sulphatide-positive lineage [1].
• Myelencephalon-specific protease (MSP), first identified in the rat and now known to have a human homologue (human kallikrein 6), is preferentially expressed in the central nervous system (CNS), compared with nonneural tissues [5].

Associations of TMPRSS13 with chemical compounds

• We show that the pro form of MSP does not self-activate but, rather, requires cleavage after lysine, indicating that mature active MSP is regulated by a distinct protease [5].
• Hence, we have identified a 202-nucleotide region within the MSPL 3'UTR that is in part responsible for cycloheximide induction [11].
• Interestingly, influenza-induced corticosterone secretion was blunted in MSP mice, suggesting that the increase in immune reactivity to the virus was due to lack of glucocorticoid feedback control [13].
• Frequencies of the mutated alleles were found to be 2.5% (Rsal), 7.9% (Dral), and 8.7% (Mspl) in controls; 4%, 14.1%, and 12% in alcoholics without clinical symptoms; and 3.1%, 12.5%, and 11.2% in alcoholics with ethanol-related diseases [14].
• 6. It was concluded that the tannin content of MSP is high and it appeared to be bound with other nutrients thereby reducing their availability [15].

Analytical, diagnostic and therapeutic context of TMPRSS13

• To accurately assess promoter hypermethylation for many genes simultaneously in small samples, we developed a novel method, quantitative multiplex-methylation-specific PCR (QM-MSP) [16].
• By immunohistochemical localization, MSP was present at moderate to high levels in neurons and oligodendroglia of the adult human brain, at a level closely resembling the relative abundance indicated by Northern blot [17].

References