Transmembrane protease serine 2: Difference between revisions
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Prostate cancer (PC) is the most common form of cancer found in American men and the second leading cause of cancer death. <ref>DOI 10.4172/1948-5956.1000119</ref> This means that approximately 28.5% of cancers and 3.5% of cancer related deaths in men are due to PC. | Prostate cancer (PC) is the most common form of cancer found in American men and the second leading cause of cancer death. <ref>DOI 10.4172/1948-5956.1000119</ref> This means that approximately 28.5% of cancers and 3.5% of cancer related deaths in men are due to PC. | ||
The most prevalent chromosomal aberration causing this pathology is the fusion of the the promoter of transmembrane protease serine 2 (TMPRSS2) gene and the coding sequence of the erythroblastosis virus E26 (Ets) gene family members. <ref>DOI 10.1126/science.1117679</ref> Ets family members are oncogenic transcription factors. <ref>DOI 10.1038/sj.onc.1201868</ref> Therefore, the fusion of these genes leads to the production of Ets transcription factors under the control of the androgen sensitive promoter elements of TMPRSS2. Specifically, the TMPRSS2-ERG fusion has been identified in approximately 50% of PC cases. <ref>DOI 10.1016/j.ccr.2010.03.018</ref> | The most prevalent chromosomal aberration causing this pathology is the fusion of the the promoter of transmembrane protease serine 2 (TMPRSS2) gene and the coding sequence of the erythroblastosis virus E26 (Ets) gene family members. <ref>DOI 10.1126/science.1117679</ref> Ets family members are oncogenic transcription factors. <ref>DOI 10.1038/sj.onc.1201868</ref> Therefore, the fusion of these genes leads to the production of Ets transcription factors under the control of the androgen sensitive promoter elements of TMPRSS2. Specifically, the TMPRSS2-ERG fusion has been identified in approximately 50% of PC cases, responsible for driving carcinogenesis. <ref>DOI 10.1016/j.ccr.2010.03.018</ref> | ||
This mutation occurs through chromosomal translocation or intergenic deletion, with both genes on the same arm of chromosome 21, and results in overexpression of chimeric mRNA of ERG in response to androgens. There is impairment of apoptosis in TMPRSS2-ERG positive cancer cells, possibly due to disruption of the intracellular death domain or decoy receptors. <ref>DOI 10.1186/1475-2867-14-34 </ref> | This mutation occurs through chromosomal translocation or intergenic deletion, with both genes on the same arm of chromosome 21, and results in overexpression of chimeric mRNA of ERG in response to androgens. There is impairment of apoptosis in TMPRSS2-ERG positive cancer cells, possibly due to disruption of the intracellular death domain or decoy receptors. <ref>DOI 10.1186/1475-2867-14-34 </ref> | ||
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=== Viral entry === | === Viral entry === | ||
'''TMPRSS2''' facilitates the entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins. As human TMPRSS2 is expressed in cells of the respiratory tracts, in addition to the epithelia of the gastrointestinal and urogenital systems, it mediates the entry of several viruses related to respiratory diseases into the host cells, including Influenza virus and the human coronaviruses HCoV-229E, MERS-CoV, SARS-CoV and SARS-CoV-2 (COVID-19 virus). | '''TMPRSS2''' facilitates the entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins (viral spike protein). As human TMPRSS2 is expressed in cells of the respiratory tracts, in addition to the epithelia of the gastrointestinal and urogenital systems, it mediates the entry of several viruses related to respiratory diseases into the host cells, including Influenza virus and the human coronaviruses HCoV-229E, MERS-CoV, SARS-CoV and SARS-CoV-2 (COVID-19 virus). | ||
====SARS-CoV-2==== | ====SARS-CoV-2==== | ||
