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page 4 17.) What aro the two mechanisms of regulating enżyme production outlined In this diagram. Genes encode anzymes Precursor 18.) Tryptophan Tumor suppressor genes normally inhibit cell division. 19.) Which of the statements are a function of the tumor suppressor genes A.) repair damage DNA B.) control cell adhesion C.) act in cell signaling pathway to inhibit the cell cycle 20.) What is the function of the RAS gene? 21.) Bonus What is the function of the P-53 gene? AJJSci251Quiz 17,18Camp Doge 4

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17. Tryptophan(final product) is inhibiting the first enzyme of the pathway. This type of regulation is called feedback inhibition. Tryptophan must be binding to an allosteric site on enzyme 1.

18. This type of regulation is repression of gene expression also called feedback regulation .The end product of the pathway is acting at the gene level by repressing the expression of gene producing enzyme 2 of the pathway.

19 Tumor suppressor genes have the all functions A,B and C. BRCA1 and BRCA2 are involved in DNA repair. One of the key feature of tumor is metastasis in which cells break contacts with adjacent cells and migrate to distant sites. So cell adhesion molecules also serve as tumor suppressor because a mutation in them can cause metastasis. Example of cell adhesion gene is E-cadherin. Some tumor suppressor also inhibit cell cycle progression in response to DNA damage. Example: PTEN is a tumor suppressor gene whose product is a phosphatase involved in regulation of cell cycle. It negatively regulates PI3K pathway signalling pathways which is involved in cell growth, survival and migration.

20. RAS gene is an oncogene. Its gene product regulates variety of functions like cell proliferation, differentiation, adhesion, apoptosis and migration. RAS gene encodes for a G ( guanine nucleotide binding) protein. Ras protein participates in mitogenic signal transduction downstream of a various growth factor receptors. When G protein binds to GTP it is activated whereas if it binds to GDP it is inactive. Guanine nucleotide exchange factor (GEF) stimulates the exachange of GTP for GDP. GTPase activating protein (GAP) hydrolyzis Ras bound GTP converting it to inactive form.

Activated Ras binds to Raf kinase which phosphorylates and activates downstream signalling molecule MEK. MEK then activates ERK by phosphorylation. Activated ERK phosphorylates other cytoplasmic and nuclear proteins. In the nuclear ERK activates Elk-1 trancription factor leading to transcriptional activation of 100 genes called immediate- early genes. Some immediate early genes code for transcription factors which then activate transcription of secondary genes.

21. p53 is a tumor suppressor gene involved in DNA repair process. It inhibits cell cycle progession until DNA damage is repaired. It can also mediates apoptosis in response to DNA damage. The function of p53 depends on the extent of DNA damage.

In response to DNA damage activation of ATM and CHK kinase takes place. These kinases activate p53 by phosphorylation. p53 activates expression of its target genes. One such target gene product include Cdk inhibitor p21, which inhibits Cdk1/ cyclin and Cdk2/ cyclin, thereby stopping cell cycle progression. p53 halts the cell cycle at G1 phase. This halt allows cell to repair its DNA. If all repair is done, cell progesses through the cycle. If there is still some damage left, cells undergo apoptosis

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