Chapter 9 Flashcards
Draw the cell cycle including the phases of the cell cycle and the quiescent phase.
Include the nb cyclin/cdk groups and their key inhibitors. Label the restriction point.
..
Cyclins bind to CDKs to activate them. Overexpression of CDKi’s (INKs/KIPs) can lead to arrest in what phase of the cell cycle?
Name 3 examples of each group. Which group is ONLY active in G1?
Overexpression of KIPs or INKs - G1 arrest
KIPs - p21, p27, p57
INKs - p15, p16, p18, p19
INKs only work in G1, KIPs active in ALL phases
What is the function of cdc25 mols (A-C)?
cdc - cell division cycle phosphatases remove the inhibitory phosphatases from cdks; this is required for complete cdk activation.
Review the enzymes involved in targeting the proteins for the ubiquitin pathway and their function
3 enzymes:
E1 - ubiquitin activating enzyme mediates attachmt of substrate to Ub
E2 - Ub conjugating enzyme
E3 - ubiquiting ligase which is the one that tags it to a specific protein
Which 3 cyclins are reported to be involved in the G1-S transition?
What protein is nb at the R point?
Is it hypo or hyper phosphorylated when active?
When it is active is there or is there not cell cycle progression?
If easier, just describe how it works!
At what phases in the cell cycle is this protein hypo and hyperphosphorylated?
Cyclins D, E, and A
Rb - if hyperphos, inactive so cannot bind E2F so E2F is free to act as transcription factor and cell cycle progression occurs.
When Rb is hypophosphorylated, it binds E2F and also recruits histone deacytylases (which when active keep DNA coiled preventing transcription).
Hypophosphorylation occurs in M phase, Hyperphosphorylation in G1.
Which 2 cyclins are nb in G2-M transition?
B and A
p21 is upregulated by what key regulatory protein?
In response to what stimuli?
p21 is also nb in the regulation of non-proliferating cells that are trying to do what?
p53
cellular stress or DNA damage
differentiate
which CDKi has been shown to be critical in cellular senescence?
P16/INK4
Myc acts as a _____ that works with its dimerization partner ____ to regulate cell proliferation. If Myc expression is constitutively active, cell cycle occurs despite _________. Myc negatively inhibits which 3 cell cycle inhibitors? And positively influences what 2 pro-cell cycle progression molecules?
transcription factor Max absence of growth factors p15, p21, p27 cyclin D and cdc25A
Ras is nb for cell cycle progression at what phase(s) of the cell cycle?
Ras triggers what two intracellular signaling pathways?
All phases
MAPK pathway and P13K pathway both which result in increased cyclin D expression
The deregulation of cell cycle control in cancer can be due to upregulation of positive effectors on the cell cycle such as (name 2)
OR due to downregulation of negative effectors such as (name 1)
cyclins
cdc25 phosphatases
CYCLIN E1 is the best px indicator
CDKi’s
INKs are much more commonly affected th KIPs
p21 can be downregulated bc of faulty p53
Flavopiridol is what type of new drug (what is MOA)?
potent inhibitor of CDKs 1,2,4
Explain exponential growth
Implies that the time the tumor takes to double its volume is constant. Often leads to the false impression that the rate of tumor growth is accelerating over time.
A number of generalizations have been made about tumor growth. Fill in the blanks.
There is ___ variation in growth rate among tumors of the same histologic site and site of origin. In humans, mean doubling times in lung mets in common tumors generally ranges from ___ months.
How many tumor doublings must an avg human solid tumor undergo before it achieves a detectable size at a weight of 1 gram (10^9 cells = 1 billion)?
wide
2-3
30-33
Draw the gompertzian growth curve. Be sure to describe the 3 phases of growth and label the axes of the curve.
figure 9.11 p 181
X axis time. Y axis cell #
sigmoidal
Preclinical phase (latent) - likely fastest growth
Limit of clinical detection - 10^9
Clinical growth
