intro_s9

intro_s9 - The retinoblastoma and p53 pathways are...

Info iconThis preview shows pages 1–4. Sign up to view the full content.

View Full Document Right Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: The retinoblastoma and p53 pathways are inactivated in most, if not all, cancer cells (Figure by MIT OCW.) How p53 and Rb pathway function may be disrupted in cancer cells Components of the pathway which are found altered in human cancers are shown in red on the diagram above. p53 and Rb themselves may be inactivated by gene mutation (loss of both copies or also as in familial retinoblastoma and Li-Fraumeni syndrome where there are inherited mutations in one copy of Rb or p53 gene respectively. Alternatively, inactivation of the p53 and Rb proteins via the action of HPV oncoproteins E6 and E7 respectively. Gene mutation may lead to the production of "activated Ras" which signals continuously. Gene amplification or overexpression may lead to overproduction of Myc, again promoting the cell cycle. Overexpression of cyclin D1 (eg by gene amplification) is found in some tumours. p16 loss by gene mutation (both copies) - note familial melanoma syndrome where there is an inherited mutation in one copy of p16 gene. Overexpression of MDM2 protein (E3 ligase controlling the levels of p53), eg by gene amplification, will lead to increased instability of p53 protein. A mutation in the apoptotic pathway downstream of p53 will block the induction of programmed cell death by p53. (Figure by MIT OCW.) Human papilloma virus (HPV) (Image removed due to copyright considerations.) ) infects epithelial cells causing warts. It is a sexually- transmitted disease and can form these lesions in the anogenital tracts (known as condyloma accuminata). There are several forms of HPV that vary on their malignancy. Some only produce the warts (as HPV-6 and 7) whereas others, such as HPV-16 and 18 are associated to malignant lesions such as cervical cancer . These malignant forms encode the oncoproteins E6 and E7 both able to bind cell regulatory proteins: p53 (E6) and pRB (E7). HPV (human papilloma virus) In the case of E6, this oncoprotein is able to interact with a cellular E3 protein ligase (E6-AP) so it ubiquitinates p53. E6 enhances p53 degradation, preventing the infected cell from undergoing apoptosis so the virus can then ensure its own proliferation. Similarly, E7 also prevents programmed cell death by destabilization of pRB. Thats one of many reasons why its so important to use sexual protection and to go through regular Pap smear check-ups if you are a woman. Direct contact with the warts can transmit the disease. Men can also develop anal cancer through HPV infection....
View Full Document

This note was uploaded on 11/11/2011 for the course BIO 7.344 taught by Professor Bobsauer during the Spring '08 term at MIT.

Page1 / 7

intro_s9 - The retinoblastoma and p53 pathways are...

This preview shows document pages 1 - 4. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online