lecture 11

Question 1

What are the 3 stages of Rb in the G1 cell cycle?
What does Rb do and how does it do it? What class of protein is Rb?

Answer 1

• unphosphorelation, hypophosphorelation and hyperphosphorelation. Rb allows for control of the R-point, it is classed as a tumor suppressor.

Question 2

How does Rb go from unphosphorelated, to hypo and hyper state and what is the ultimate consequence of this?

Answer 2

first phosphorelated by D-4/6 complex then by E-2 complex, now it is hyperphosphorelated and inactive. Cannot bind to E2F/DP complex and allows cell to pass R-point

Question 3

How does hypophosphorelated Rb do its job?

Answer 3

Recruits HDAC to increase histone–> DNA binding and binds to E2F/DP complex and prevents it to function on the genome to signal transcription and lead the cell through R-point.

Question 4

How does hyperphosphorelated Rb not do its job

Answer 4

Cant bind to E2f and DP, also recruits acetyl groups to reduce histone/DNA interaction, more transcription, R-point passed

Question 5

Discuss how cyclin E may lead to oncogenic activity if it is not regulated

Answer 5

i may degrade p27 by phosphorelating it and targeting it for destruction by proteosomes via ubiquitylation

Question 6

How does Ras cause production of D cyclin

Answer 6

Fos/Jun or B catenin

Question 7

What happens when Myc/Max form a complex and bind to DNA, same for Mxd and Max

Answer 7

• proliferation by increasing cyclin, E2F levels and decreasing p21,p27,p57,p15,p16,p18,p19
• differentiation

Question 8

Give an antiproliferative example of TGF-beta

Answer 8

• inhibits E2F and Myc, also produces CDKI’s