Sandbox Reserved 167: Difference between revisions
No edit summary |
|||
| (16 intermediate revisions by the same user not shown) | |||
| Line 11: | Line 11: | ||
P16INK4a is an oncoprotein | P16INK4a is an oncoprotein or known tumor suppressor when over-expressed within the cell-progression pathway of the retinoblastoma protein (pRB). It is a cyclin-dependent kinase inhibitor that will negatively affect proliferation of a natural cell cycle. <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>. The effectiveness of the over-expression occurs between the G1 and S phases of the cell cycle, making it significantly important in the stability of proliferation vs. growth arrest of the cell during the cell cycle. P16INK4's ability to inhibit phosphorylation of the cdk4/6 shifts the balance of pRB not binding to E2F (inactivity) to the binging of pRB to E2F, also known as functional. <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>. The release of E2F from pRB ceases the blocking mechanism of transcription of P16INK4a, leading to the over-expression of functional p16INK4a. Reasoning provides an over-expression of p16INK4a is associated with the presence of Human Papillomavirus. <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> | |||
== Role In Cervical Cancer == | == Role In Cervical Cancer == | ||
P16INK4a | 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 | |||
lesions progression risk.Romanian Journal of Morphology and Embryology 2010, 51(3):497–503 </ref> E7 directly affects 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 == | ||
The structure of p16INK4a is tertiary with four helix-turn-helix motifs linked by three loops. <ref name="Byeon"> Byeon, I.J., Li, J., Ericson, K., Selby, T.L., Tevelev, A., Kim, H.J., O`Maille, P., Tsai, M.D. Tumor suppressor p16INK4A: determination of solution structure and analyses of its interaction with cyclin-dependent kinase 4.(1998) Mol.Cell 1: 421-431 PMID: 9660926 </ref>. | |||
Important recognition binding units have been identified on both p16INK4a and cdk4/6, including a region of 58 residues at cdk4's n terminus for the binding of p16INK4. P16INK4a is a polypeptide chain made up of 156 units, with multiple mutant chains having been synthetically derived. <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>. | |||
== Future Importance of P16INK4a == | == Future Importance of P16INK4a == | ||
P16INK4a has been discovered to be an important biological marker for the presence of high-rish Human Papillomavirus in patients because of its over-expression due to the disruption of the binding mechanism between the transcription factor E2F and pRB.<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>. P16INK4a is an independent factor from the HR-HPV type and therefore can be used to detect the presence of cervical cancer disease when tested for among HR-HPV and non-HPV patients.<ref name="Byeon"> Byeon, I.J., Li, J., Ericson, K., Selby, T.L., Tevelev, A., Kim, H.J., O`Maille, P., Tsai, M.D. Tumor suppressor p16INK4A: determination of solution structure and analyses of its interaction with cyclin-dependent kinase 4.(1998) Mol.Cell 1: 421-431 PMID: 9660926 </ref>. Oncogenic activity among all types of HPV patients can be identified with the blocking of pRB by E7 and the over-expression of p16INK4a caused by this inhibition. Testing for the presence of the over-expression of p16INK4a in pre-cancerous and cancerous individuals is easy and efficient and has become increasingly used among doctors alike. | |||
== References == | == References == | ||
<references /> | |||