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| - | P16INK4a is an | + | P16INK4a is an anti-oncogene 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 effect 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. | 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. | ||
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== 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>. The oncoproteins <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>. |
== 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>. | 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. | ||
== 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>. | ||
== References == | == References == | ||
<references /> | <references /> | ||
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'P16INK4a'
Contents |
Background
P16INK4a is an anti-oncogene 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 effect proliferation of a natural cell cycle. [1]. 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.
Role In Cervical Cancer
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. [2]. The oncoproteins [3].
Structure of Protein
The structure of p16INK4a is tertiary with four helix-turn-helix motifs linked by three loops. [4]. 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.
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. [2].
References
- ↑ 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
- ↑ 2.0 2.1 Silverman, Robert, RPh, MM and Ridder, Dr. Rüdiger. p16INK4a Antibody. MTM Laboratories Website. http://mtmlabs.com/us/index.php/science-a-technology/p16ink4a
- ↑ 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.
- ↑ 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
