Este xene codifica unha proteína que pertence á familia das serina proteases. A proteína codificada contén un dominio transmembrana de tipo II, un dominio receptor de clase A, un dominio receptor scavenger rico en cisteína e un dominio de protease. As serina proteases están implicadas en moitos procesos fisiolóxicos e patolóxicos. Este xene está regulado á alza por hormonas androxénicas nas células de cancro de próstata e regulado á baixa en tecidos de cancro de próstata independente de andróxenos. O dominio de protease desta proteína pénsase que é cortado e segregado no medio celular despois da súa autoclivaxe. A función biolóxica deste xene é descoñecida.[2]
A función da proteína TMPRSS2 na carcinoxénese de próstata baséase na sobreexpresión de factores de transcrición ETS, como ERG e ETV1, por medio de fusión xénica. O xene de fusión TMPRSS2-ERG é o máis frecuente, presente no 40% - 80% dos cancros de próstata humanos. A sobreexpresión de ERG contribúe ao desenvolvemento de cancros de próstata independentes de andróxenos por medio da disrupción da sinalización do receptor de andróxenos.[3]
Relación cos coronavirus
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Algúns coronavirus, por exemplo o SARS-CoV, causante da SARS, e o SARS-CoV-2, causante da COVID-19, son activados por TMPRSS2 e poderían ser inhibidos por inhibidores de TMPRSS2.[4] "O SARS-CoV-2 usa o receptor ACE2 do SARS-CoV para a entrada e a serina protease TMPRSS2 para o cebado da proteína S. Un inhibidor da TMPRSS2 aprobado para uso clínico bloqueou a entrada e podería constituír unha opción de tratamento."[4]
- ↑ 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. PMID 9325052. doi:10.1006/geno.1997.4845.
- ↑ 2,0 2,1 "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. PMC 2874722. PMID 20478527. doi:10.1016/j.ccr.2010.03.018.
- ↑ 4,0 4,1 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. PMID 32142651. doi:10.1016/j.cell.2020.02.052. Resumo divulgativo – Deutsches Primatenzentrum GmbH.
- 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. PMID 8125298. doi:10.1016/0378-1119(94)90802-8.
- 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. PMID 9373149. doi:10.1016/S0378-1119(97)00411-3.
- 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. PMID 11169526. doi:10.1002/1096-9896(2000)9999:9999<::AID-PATH743>3.0.CO;2-T.
- 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. PMID 11322890. doi:10.1046/j.1432-1327.2001.02165.x.
- 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. PMID 11414763. doi:10.1006/geno.2001.6551.
- 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. PMC 1183478. PMID 15537383. doi:10.1042/BJ20041066.
- 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. PMID 16575875. doi:10.1002/gcc.20329.
- 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. PMID 16585160. doi:10.1158/0008-5472.CAN-06-0168.
- 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. PMC 1601467. PMID 16820092. doi:10.1593/neo.06283.
- 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. PMC 1617224. PMID 16973594. doi:10.1128/JVI.01118-06.
- 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. PMC 1715930. PMID 17032499. doi:10.1593/neo.06427.
- 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. PMID 17367471. doi:10.1111/j.1600-0463.2007.apm_652.x.
- 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. PMID 17390040. doi:10.3892/or.17.5.1033.
- 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. PMID 17632455. doi:10.1038/modpathol.3800903.
