TUMOR SUPPRESSING FUNCTIONS OF p16INK4a - A REVIEW
<p>DNA damage can have particularly severe carcinogenic influence if it incapacitates the cellular machinery normally protecting the cell from the effects of genomic damage. The protective functions involve not only DNA repair and apoptosis (programmed cell death), but also regulation of the c...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Faculty of Dentistry, Universitas Indonesia
2015-07-01
|
| Series: | Journal of Dentistry Indonesia |
| Subjects: | |
| Online Access: | http://jdentistry.ui.ac.id/index.php/JDI/article/view/469 |
| Summary: | <p>DNA damage can have particularly severe carcinogenic influence if it incapacitates the cellular machinery normally protecting the cell from the effects of genomic damage. The protective functions involve not only DNA repair and apoptosis (programmed cell death), but also regulation of the cell cycle and proliferation. Therefore, carcinogenesis can be promoted by inactivating or altering key regulatory proteins like p16<sup>INK4a </sup>which has the capability to arrest the cell cycle in the G<sub>1 </sub>phase and prevent inappropriate proliferation. Functionl cyclin- dependent kinase (Cdk) inhibitor p16<sup>INK4a </sup>binds to Cdk-4 and Cdk-6 thereby preventing Cdk-cyclin complexes from promoting phosphorylation of pRb and releasing the transcription factor E2F needed for the cell cycle to proceed to the S phase. Arrest in G<sub>1</sub><span style="font-size: 8px;"> </span>accounts for a minority of arresting cells after DNA damage, the majority of arrests taking place in G<sub>1 </sub>without recognized p16<sup>INK4a </sup>contribution. However, inactivating alterations of p16<sup>INK4a </sup>are common in cancers, possibly because of additional functions of p16<sup>INK4a </sup>in senescence and inhibition of the spreading and migration of cancer cells. Since oncogenic initiation is insufficient for growing significant tumors without spreading and angiogenesis, this could partly expain why inactivated p16<sup>INK4a </sup>is frequently exhibited in clinical tumors in spite of apparently less exclusive role in cell cycle arrest.On the other hand, multiple oncogenic events are usually necessary to develop cancer and generally both pRb and p53 pathways are impaired in tumors. This suggests that growth regulation in G<sub>1 </sub>and therefore also its key molecular components including p16<sup>INK4a </sup>are important in carcinogenesis.</p><p><span style="font-size: 8px;"><br /></span></p> |
|---|---|
| ISSN: | 1693-9697 2355-4800 |