9/20 Tumor suppressor genes

Question 1

haploinsufficiency

Answer 1

having one mutant allele can also result in cancer so it doesn’t necessarily require two alleles to cause issues

Question 2

p53

Answer 2

latent in normal cells bound to Mdm2 (also an oncogene) activated in response to DNA damage/stress signal. regulates transcription of p21 (a CKI). p21 inhibits G1 cdk/cyclin complex. blocks G1/S

Question 3

describe p53 dna damage pathway

Answer 3

ATM and Chk2 are activated and phosphorylize p53 preventing it binding to Mdm2.

Question 4

describe cell stress on p53 pathway

Answer 4

ATR and Casein kinase II are activated and phosphorylyze p53 so it cant bind to MDM2

Question 5

describe oncogene activation of p53 pathway

Answer 5

pp14arf is activated (not a kinase) it binds to MDM2 and blocks it from associating with p53 (by sequestering it and moving it to nucleolus)

Question 6

describe adenomatous polyposis coli (APC) gene

Answer 6

TSG involved in signal transduction and cell architecture. associated with FAP, and autosomal genetic disease that results in multiple polyps in colon and rectum that eventually lead to carcinoma. APC is responsible for disorder

Question 7

give more info on APC gene

Answer 7

mapped to chromosome 5. 300 kDa protein

Question 8

describe APC pathway

Answer 8

normally APC bound to GSK and beta-catenin. this binding taragets beta-catenin for intracellular destrution through ubiquitin mediated pathways. if no APC around then high levels of beta-catenin persists. beta-catenin at adherens junctions and also serves as a transcription factor. targets are still unknown; likely gene products that promote proliferation or inhibit cell death

Question 9

describe BRCA1 gene

Answer 9

TSG involved in control of gene expression. up to 1 in 8 women will be diagnosed with breast cancer. 1-2% of cases involved inherited mutation in BRCA1 or BRCA2 genes mapped to chromosome 17. in hereditary forms of breast cancer BRCA1 mutated 45% and in ovarian cancer 80%

Question 10

what is the function of BRCA1

Answer 10

it is a cellular response to DNA damage. it induces dna repair during replication.

Question 11

describe Wilms Tumor (WT) gene

Answer 11

pediatric tumor of the kidney. 1/10,000. maps to chromosome 11 and is 50 kilbases with 10 exons. alternatively spliced into 4 different products. transcriptional regulator. the tumor is a nephroblastoma

Question 12

what are zinc fingers

Answer 12

a motif that means its a protein binding motif. thus you can know that it is a transcriptional regulator. however i is the end piece that actually regulates.

Question 13

where is wilms tumor developed

Answer 13

in kidney spleen or gonads.