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P16INK4a has been positively correlated to high-risk Human Papillomavirus(HR-HPV)because it inhibits the phosphorylating activity associated with the cdk4/6 - cyclin D complex and the counterparts, retinoblastoma protein (pRB) and the transciption factor E2F. Progression of the cell cycle is controlled by the pRB pathway and its ability to bind to the transciption factor E2F to block the transcription of genes that promote cell proliferation. The pRB pathway is critical for the maintenance of balance between cell cycle continuous and cell cycle rest. <ref name="Silverman"> Silverman, Robert, RPh, MM and Ridder, Dr. Rüdiger. p16INK4a Antibody. MTM Laboratories Website. http://mtmlabs.com/us/index.php/science-a-technology/p16ink4a </ref>. An analysis done by Tsoumpou et al. found that over-expression of P16INK4a increased among cervical smears as cell abnormality increased. <ref name="TSOUMPOU">TSOUMPOU I, ARBYN M, KYRGIOU M, WENTZENSEN N, KOLIOPOULOS G, MARTIN-HIRSCH P, MALAMOU-MITSI V, PARASKEVAIDIS E.  p16INK4a immunostaining in cytolo-gical and histological specimens from the uterine cervix: a systematic review and meta-analysis, Cancer Treat Rev, 2009, 35(3):210–220.</ref>. Therefore, the presence of this oncoprotein has major prevalence among HPV and Cervical cancer patients.  
P16INK4a has been positively correlated to high-risk Human Papillomavirus(HR-HPV)because it inhibits the phosphorylating activity associated with the cdk4/6 - cyclin D complex and the counterparts, retinoblastoma protein (pRB) and the transciption factor E2F. Progression of the cell cycle is controlled by the pRB pathway and its ability to bind to the transciption factor E2F to block the transcription of genes that promote cell proliferation. The pRB pathway is critical for the maintenance of balance between cell cycle continuous and cell cycle rest. <ref name="Silverman"> Silverman, Robert, RPh, MM and Ridder, Dr. Rüdiger. p16INK4a Antibody. MTM Laboratories Website. http://mtmlabs.com/us/index.php/science-a-technology/p16ink4a </ref>. An analysis done by Tsoumpou et al. found that over-expression of P16INK4a increased among cervical smears as cell abnormality increased. <ref name="TSOUMPOU">TSOUMPOU I, ARBYN M, KYRGIOU M, WENTZENSEN N, KOLIOPOULOS G, MARTIN-HIRSCH P, MALAMOU-MITSI V, PARASKEVAIDIS E.  p16INK4a immunostaining in cytolo-gical and histological specimens from the uterine cervix: a systematic review and meta-analysis, Cancer Treat Rev, 2009, 35(3):210–220.</ref>. Therefore, the presence of this oncoprotein has major prevalence among HPV and Cervical cancer patients.  
E6 and E7 are two viral oncoproteins whose interaction with regulatory host genes leads to the disruption of the cell cycle; a direct effect of HPV. <ref name="Ungureanu"> Ungureanu, Carmen, Socolov, Demetra, Anton, Gabriela, Miahailovici, Maria Sultana, and Teleman, S. Immunocytochemical expression of p16INK4a and HPV L1 capsid proteins as predictive markers of the cervical
E6 and E7 are two viral oncoproteins whose interaction with regulatory host genes leads to the disruption of the cell cycle; a direct effect of HPV. <ref name="Ungureanu"> Ungureanu, Carmen, Socolov, Demetra, Anton, Gabriela, Miahailovici, Maria Sultana, and Teleman, S. Immunocytochemical expression of p16INK4a and HPV L1 capsid proteins as predictive markers of the cervical
lesions progression risk.Romanian Journal of Morphology and Embryology 2010, 51(3):497–503 </ref>
lesions progression risk.Romanian Journal of Morphology and Embryology 2010, 51(3):497–503 </ref> E7 directly effects the Impairment of the function of pRB by inhibiting the binding of pRB to E2F, causing an increase in levels of E7 and transciption of genes that promote cell proliferation. <ref name="Silverman"> Silverman, Robert, RPh, MM and Ridder, Dr. Rüdiger. p16INK4a Antibody. MTM Laboratories Website. http://mtmlabs.com/us/index.php/science-a-technology/p16ink4a </ref>.


== Structure of Protein ==
== Structure of Protein ==

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