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Pathobio Exam 1
Set 1: Intro
37
Pathology
Graduate
10/05/2011

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Cards

Term
What initiates normal cell replication?
Definition
GF binding to and activating its receptor => activation of signal-transduction proteins.
Term
What causes DNA transcription that promotes entrance to the cell cycle?
Definition
Signal tranduction thru the nucleus => activation of nuclear transcription regulatory factors.
Term
Function

Ras proteins
Definition
transient intracellular signal transduction
Term
How are Ras proteins activated?
Definition
GF bings to its receptor
Term
What does activated Ras stimulate?
Definition
MAP kinase cascade => nuclear signals for proliferation
Term
What binds to Ras to inactivate it & therefore terminate signal transduction?
Definition
GTPase-activating proteins (GAPs) (enhance GTP hydrolysis)
Term
Which GAP specifically is important in the termination of Ras protein signal transduction?
Definition
Neurofibromin
Term
Does Ras need GDP or GTP for activation?
Definition
GTP
Term
What does MYC encode for?
Definition
nuclear protein integral to both cell proliferation & apoptosis
Term
What are the 2 ways MYC can be activated?
Definition
1) with GF binding GF receptor => mitogenic signal transduction to the nucleus

or

2) without GF stimulation
Term
What happens in MYC is activated without GF stimulation?
Definition
cellular apoptosis
Term
How does MYC induce transcription activation?
Definition
MYC-MAX protein forms and binds to DNA
Term
What 2 things must be transcriptionally activated to enter the cell cycle?
Definition
cyclin D
CDK4 genes
Term
What are the 3 cell cycle regulators?
Definition
cyclins
CDKs (cyclin-dependent kinases)
CDK inhibitors
Term
How do CDKs become phosphoylated & activated?
Definition
inactive CDK binds to cell cycle-specific cyclins
Term
How do activated CDKs promote progression through the cell cycle?
Definition
they phosphoylate key proteins necessary
Term
What is bound to the hypophosphorylated retinoblastoma (RB) protein to inhibit it's function in G0 & G1?
Definition
E2F transcription factor complex
Term
When in the cell cycle do organelles double in number?
Definition
G1
Term
What leads to the phosphorylation of RB in G1?
Definition
synthesis of cyclin D & cyclin E => phosphorylated D/CDK & E/CDK
Term
What causes the dissociation of E2F from RB & transcriptional activation of E2F-targeted genes in G1?
Definition
phosphorylation of RB
Term
What happens in S phase of the cell cycle?
Definition
nuclear DNA is replicated
Term
What cyclin & therefore cyclin/CDK complex is formed in the S phase of the cell cycle?
Definition
A
Term
When in the cell cycle are new membrane formed in preparation for cell division?
Definition
G2
Term
What is done in G2 to initiate mitosis?
Definition
cyclin B synthesis => B/CDK
Term
What are the 5 phases of mitosis?
Definition
1)Prophase
2)Prometaphase
3)Metaphase
4)Anaphase
5)Telophase
Term
What characterizes completion of mitosis?
Definition
Removal of phosphate groups from RB which regenerates hypophosphorylated form
Term
When is the restriction point in the cell cycle?

What regulates it?
Definition
in the middle of G1 regulated by GFs
Term
Where in the cell cycle are the checkpoints for DNA damage?
Definition
G1/S & G2/M
Term
When is RB phosphorylated in the cell cycle?
Definition
in G1 prior to S phase.
Term
What do CDK inhibitor respond to?
Definition
growth suppressing signals
Term
How do CDK inhibitors block progression of the cell cycle?
Definition
inactivating cyclin/CDK complexes or inhibiting their formation
Term
Fuction G1/S Checkpoint
Definition
check for DNA defect prior to replication
Term
What happens if there's a DNA defect detected at the G1/S checkpoint?
Definition
increase levels & activation of p53 => up regulation of p21 => cell cycle arrest & stimulation of DNA repair
Term
What happens if there is a DNA defect detected in the G1/S checkpoint, and it's successfully repaired?
Definition
p53-induced transcriptional activation & formation of self-degrading protein => cell cycle resumed
Term
What happens if there is a DNA defect detected at G1/S checkpoint, but it's not repaired successfully?
Definition
p53-induced transcriptional activation of pro-apoptotic genes, repression of pro-proliferative & anti-apoptotic genes => apoptosis
Term
Function G2/M Checkpoint
Definition
check for DNA defect after replication & before separation of the chromatids
Term
What happens if there is a DNA defect detected at the G2/M checkpoint?
Definition
cell cycle arrest via p53-dependent & independent processes.
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