CDK HIV-1 Integrase protease HAT GPCR Retniblastoma

Retniblastoma / HPV

  Retinoblastoma is a herediatary pediatric neoplasm that arises from the retinal cells. The biallelic Rb mutation in retinoblastoma tumour identified shows that this gene product exerts the action of a tumour suppressor. Thus retinoblastoma plays a decisive role in the negative control of the cell cycle and in the tumour progression. This protein is responsible for the major G1 checkpoint through blocking the S-Phase entry and cell growth. The pRB protein represses the transcription of gene required for the transition from G1 to S phase by directly binding to the transactivation domain of E2F and these complex bind to the promoter or enhancer of these genes by binding directly as a complex with E2F. Loss of the pRb function induces cell cycle deregulation and also leads to a malignant phenotype. The binding of the viral oncoprotein to the retinoblastoma results in the functional inactivation of pRb which leads to the number of neoplasis such as cervical cancer, mesothelioma and AIDS related Burkitts lymphoma. Retinoblastoma was appeared to be the most important target for the cervical cancer.
Retinoblastoma associated with HPV
  Human papillomaviruses (HPVs) associated with benign lesions as well as the cervical intraepithelial neoplasia due to the high and low risk types of HPVs. HPV genomes are small and do not encode polymerases necessary for viral replication, in such case they need a host for viral replication. The oncogenes present in virus enables HPV to integrate into the cellular genome during the division of basal cells and the differentiation of basal epithelium to stratified epithelium. When the viral DNA is inside the nucleus but not bound to host DNA, it is episomal conformation, which is characteristic of low grade squamous intra epithelial lesions. When HPV DNA binds to the host cellular DNA, it is in the integrate conformation found in the high grade squamous intraepithelial lesions and invasive carcinomas. The HPV E7 oncoprotein is directly involved in the onset of cervical cancer and associates with the pRb protein and other cellular targets that promote cell immortalization and carcinogenesis.