L5 - Oncogenes and Tumour Suppressors

Question 1

Brca1: what cancers does it cause?

Answer 1

Breast mainly, ovarian later

Question 2

p53: what is it, what does it induce, what percentage of cancers is it responsible for, and what is the syndrome of being born with the p53 gene mutated called?

Answer 2

Tumour suppressor protein - controls movement from G1 to S phase, arresting movement when DNA is damaged and inducing apoptosis

p21 - a cell cycle inhibitor that binds to cyclin-CdK structures and stop cell-cycle progression

~50%

Li fraumeni syndrome

Question 3

What determines whether p53 causes a temporary stop to the cell cycle or apoptosis?

Answer 3

What stage p53 had begun its activation

G1 - DNA can be repaired and the cell cycle can continue
G2 - damaged DNA has already been produced, apoptosis to prevent it from being part of a fully functional cell

Question 4

Breast cancer: where do cancer cells metastasise to and what gene(?) is responsible for their metastasis?

Answer 4

Bones, typically

CBF-beta (research has shown that knockdown of the gene significantly reduces the metastasis to bone)

Question 5

Proto-oncogene

Answer 5

The perfectly normal form of an oncogene - once it becomes mutated (gaining a gain of function mutation), it becomes an oncogene and cancerous

Question 6

Viral use and capture of oncogenes

Answer 6

• Virus infects and reverse transcripts its genetic information and may integrate near certain proto-oncogenes (ie c-src)
• The virus may accidentally take the src gene when they are leaving the cell(?)
• The virus may use its new v-strc gene to encourage cell proliferation - higher viral production

Question 7

c-src vs v-src

Answer 7

c-src is the cellular gene, usually normal and a proto-oncogene

v-src is the viral version, and is usually the mutated oncogene

Question 8

Philadelphia chromosome

Answer 8

Chromosome 22 after t(9:22) has occurred, shorter than it should be

Question 9

Bcr-Abl fusion: what does it form, how is it different to the normal Abl form, and where is it mostly found?

Answer 9

Forms a protein that has its N-terminal Abl sequences missing and is an active tyrosine kinase, activates the Ras-pathway, and suppresses apoptosis

SH3 domain is slightly smaller as well as a large Bcr part being in the front of the Bcr-Abl protein

In those suffering from chronic myeloid leukemia (CML)

Question 10

v-Abl: is it more oncogenic then Bcr-Abl?

Answer 10

Yes, it completely removes the SH3 domain and is very oncogenic

Question 11

Why is the SH3 domain of the Abl protein so significant in cancer?

Answer 11

It stops the protien from being constitutively active

Question 12

Types of proteins associated with cancer

Answer 12

• Transcription factors
• Kinases
• Signalling molecules
• Cell death regulators

Question 13

Retinoblastoma: what is it, what does it involve, what does the mutated protein do, does it require aid, and what does it cause?

Answer 13

Tumour suppressor - transcriptional repressor

Null mutation of the RB gene

Regulates cell cycle - G0 to G1, dephosphorylation causes RB to bind to E2F and repress genes that promote entry into G1/S

Additional mutation often required - co-operativity

Malignant tumour of the developing retina