Question

3. (36 pts) Mutations of the following groups of genes are associated with cancer. Briefly describe:

1) Their normal functions, including the related signaling pathways and cell behaviors;

2) Their oncogenic roles: the effects of their mutants to cell behaviors in cancers (oncogene or tumor suppressor, gain or loss of function)

BAD/Bcl2/Bax

Rb/E2F

Cdk/cyclin

Akt/mTOR

Answer 1

Ans-1) Functions of-:

a) Bax gene

Bax gene induces the opening of the mitochondrial voltage- dependent anion channel. The upregulation of the expression of Bax gene is done by the tumor suppressor protein p53. Hence, it carries out p53 mediated apoptosis (cell death).Activation of Bax leads to mitochondrial outer membrane permeabilization.

b) Rb gene

It prevents excessive cell growth by inhibiting the cell cycle progression until a cell is ready to divide. It is also a recruiter of various chromatin remodelling enzymes such as methylases and acetylases. It is actually a multifunctional protein that binds to at least 100 other proteins. It binds and represses E2F dimers that are transcription factors which helps in pushing the cell into the S phase of the cell cycle.

Cdk gene

Cyclins play and important role in the cell cycle. Formation of complex between cyclin and Cdk results in activation of the Cdk active site. These cyclins then target the Cdks to specific subcellular locations to carry out enzymatic activities. Cyclins when bind to the dependent kinases form the maturation promoting factors which activate other proteins through phosphorylation. Such phosphorylated proteins lead to specific events in the cell cycle such as microtubule formation and chromatin remodelling.

Akt gene

Akt gene also known as protein kinase B plays a significant role in various cellular processes such as glucose metabolism,apoptosis, cell proliferation, cell migration and transcription.Akt 1 is involved in cellular survival pathways by inhibiting apoptotic processes. It is also able to induce protein synthesis pathways.Akt 2 is an important signaling molecule in the insulin signaling pathway.

2) Their oncogenic roles

Bax/ Bcl gene

It has anti-cancerous function as it plays a major role in apoptosis ( cell death). The pro- survival Bcl 2 family members act as oncogenes. Hence Bax gene potentially act as tumor suppressors. These genes induce apoptosis in cancer cells.

Rb gene

This gene also acts as a tumor suppressor. The Rb-E2F DP complex (E2 promoter binding protein dimerization partner) also attracts a histone deacetylase protein to the chromatin, reducing transcription of S phase promoting factors, further suppresing DNA and prevents uncontrolled cell growth that causes cancer.

Cdk gene

These are oncogenes. The mutated form of cyclin inhibits the cell cycle.

Akt gene

The Akt 1 gene belongs to a class of genes known as oncogenes. It plays a key role in regulating cell survival and tumor formation.