TMPRSS2
Transmembrane protease, serine 2 is an enzyme that in humans is encoded by the TMPRSS2 gene.[5][6]
Function
This gene encodes a protein that belongs to the serine protease family. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. Serine proteases are known to be involved in many physiological and pathological processes. This gene was demonstrated to be up-regulated by androgenic hormones in prostate cancer cells and down-regulated in androgen-independent prostate cancer tissue. The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. The biological function of this gene is unknown.[6]
ERG gene fusion
TMPRSS2 protein's function in prostate carcinogenesis relies on overexpression of ETS transcription factors, such as ERG and ETV1, through gene fusion. TMPRSS2-ERG fusion gene is the most frequent, present in 40% - 80% of prostate cancers in humans. ERG overexpression contributes to development of androgen-independence in prostate cancer through disruption of androgen receptor signaling.[7]
Relation to coronaviruses
Some coronaviruses, e.g. both the SARS coronavirus of 2003 and the SARS-CoV-2 are activated by TMPRSS2 and can thus be inhibited by TMPRSS2 inhibitors.[8] "SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming[9]. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option."[8]
References
- GRCh38: Ensembl release 89: ENSG00000184012 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000000385 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- Paoloni-Giacobino A, Chen H, Peitsch MC, Rossier C, Antonarakis SE (September 1997). "Cloning of the TMPRSS2 gene, which encodes a novel serine protease with transmembrane, LDLRA, and SRCR domains and maps to 21q22.3". Genomics. 44 (3): 309–20. doi:10.1006/geno.1997.4845. PMID 9325052.
- "Entrez Gene: TMPRSS2 transmembrane protease, serine 2".
- Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, et al. (May 2010). "An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression". Cancer Cell. 17 (5): 443–54. doi:10.1016/j.ccr.2010.03.018. PMC 2874722. PMID 20478527.
- Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. (March 2020). "SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor". Cell. 181 (2): 271–280.e8. doi:10.1016/j.cell.2020.02.052. PMC 7102627. PMID 32142651. Lay summary – Deutsches Primatenzentrum GmbH.
- Rahman N, Basharat Z, Yousuf M, Castaldo G, Rastrelli L, Khan H (May 2020). "Virtual screening of natural products against type II transmembrane serine protease (TMPRSS2), the priming agent of Coronavirus 2 (SARS-CoV-2)". Molecules. 25 (10): 2271. doi:10.3390/molecules25102271. PMC 7287752. PMID 32408547.CS1 maint: display-authors (link)
Further reading
- 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.
- 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.
- Lin B, Ferguson C, White JT, Wang S, Vessella R, True LD, et al. (September 1999). "Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2". Cancer Research. 59 (17): 4180–4. PMID 10485450.
- Vaarala MH, Porvari KS, Kellokumpu S, Kyllönen AP, Vihko PT (January 2001). "Expression of transmembrane serine protease TMPRSS2 in mouse and human tissues". The Journal of Pathology. 193 (1): 134–40. doi:10.1002/1096-9896(2000)9999:9999<::AID-PATH743>3.0.CO;2-T. PMID 11169526.
- Afar DE, Vivanco I, Hubert RS, Kuo J, Chen E, Saffran DC, et al. (February 2001). "Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia". Cancer Research. 61 (4): 1686–92. PMID 11245484.
- Jacquinet E, Rao NV, Rao GV, Zhengming W, Albertine KH, Hoidal JR (May 2001). "Cloning and characterization of the cDNA and gene for human epitheliasin". European Journal of Biochemistry. 268 (9): 2687–99. doi:10.1046/j.1432-1327.2001.02165.x. PMID 11322890.
- Teng DH, Chen Y, Lian L, Ha PC, Tavtigian SV, Wong AK (June 2001). "Mutation analyses of 268 candidate genes in human tumor cell lines". Genomics. 74 (3): 352–64. doi:10.1006/geno.2001.6551. PMID 11414763.
- Wilson S, Greer B, Hooper J, Zijlstra A, Walker B, Quigley J, Hawthorne S (June 2005). "The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells". The Biochemical Journal. 388 (Pt 3): 967–72. doi:10.1042/BJ20041066. PMC 1183478. PMID 15537383.
- Soller MJ, Isaksson M, Elfving P, Soller W, Lundgren R, Panagopoulos I (July 2006). "Confirmation of the high frequency of the TMPRSS2/ERG fusion gene in prostate cancer". Genes, Chromosomes & Cancer. 45 (7): 717–9. doi:10.1002/gcc.20329. PMID 16575875.
- Tomlins SA, Mehra R, Rhodes DR, Smith LR, Roulston D, Helgeson BE, et al. (April 2006). "TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer". Cancer Research. 66 (7): 3396–400. doi:10.1158/0008-5472.CAN-06-0168. PMID 16585160.
- Yoshimoto M, Joshua AM, Chilton-Macneill S, Bayani J, Selvarajah S, Evans AJ, et al. (June 2006). "Three-color FISH analysis of TMPRSS2/ERG fusions in prostate cancer indicates that genomic microdeletion of chromosome 21 is associated with rearrangement". Neoplasia. 8 (6): 465–9. doi:10.1593/neo.06283. PMC 1601467. PMID 16820092.
- Böttcher E, Matrosovich T, Beyerle M, Klenk HD, Garten W, Matrosovich M (October 2006). "Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium". Journal of Virology. 80 (19): 9896–8. doi:10.1128/JVI.01118-06. PMC 1617224. PMID 16973594.
- Cerveira N, Ribeiro FR, Peixoto A, Costa V, Henrique R, Jerónimo C, Teixeira MR (October 2006). "TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy number changes in prostate carcinomas and paired HGPIN lesions". Neoplasia. 8 (10): 826–32. doi:10.1593/neo.06427. PMC 1715930. PMID 17032499.
- Yoo NJ, Lee JW, Lee SH (March 2007). "Absence of fusion of TMPRSS2 and ETS transcription factor genes in gastric and colorectal carcinomas". APMIS. 115 (3): 252–3. doi:10.1111/j.1600-0463.2007.apm_652.x. PMID 17367471.
- Winnes M, Lissbrant E, Damber JE, Stenman G (May 2007). "Molecular genetic analyses of the TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in 50 cases of prostate cancer". Oncology Reports. 17 (5): 1033–6. doi:10.3892/or.17.5.1033. PMID 17390040.
- Tu JJ, Rohan S, Kao J, Kitabayashi N, Mathew S, Chen YT (September 2007). "Gene fusions between TMPRSS2 and ETS family genes in prostate cancer: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues". Modern Pathology. 20 (9): 921–8. doi:10.1038/modpathol.3800903. PMID 17632455.
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