Upgrade to remove ads
Cell Cycle 1+2
Terms in this set (36)
Resting phase, cell is metabolically active but not working towards replication
Permanent G0 phase; cell can no longer replicate
(different from post-mitotic)
Cells differentiate, grow and prepare for DNA synthesis and cell division
Checkpoint between G1 and S phases
Point of no return - once past this point the cell is committed to dividing
Only way to stop cell division after this point is through apoptosis
DNA replication occurs
Continued growth and preparation for mitosis
Mitosis. Can be subdivided into prophase, prometaphase, metaphase, anaphase, telophase, and cytokinesis.
How do cyclins and CDKs work to control the timing of events in the cell cycle?
Cyclins and CDKs = cell cycle's clock
Cyclins pair up with corresponding CDK to activate them
CDKs are always present, cyclins are transient
CDKs and cyclin for G1
CDK4 and 6
CDK and cyclin for G1/S
CDK and cyclin for S
CDK and cyclin for M
What occurs during G1 to cause the formation of cyclin D?
Growth factors - stimulate production of TFs for G1
Activate G1 CDKs by cyclins later on
Cell-matrix junctions can contribute
Which transcription factor binds to the promotor of the cyclin D gene to initiate its transcription?
List the steps of CDK/cyclin activity in G1 up to the the production of cyclin E.
Cyclin D binds to CDK 4/6
Cyclin/CDK complex gets phosphorylated by stimulatory kinases (CAK)
Activated CDK 4/6 phosphorylates Rb
Rb-E2F complex dissociates
Free E2F stimulates production of cyclin E
List the steps of CDK/cyclin activity in G1/S up to the production of cyclin A.
Free E2F stimulates cyclin E production
Cyclin E activates CDK2
CDK2 hyperphosphorylates Rb (positive feedback)
When enough E2F is released, cyclin A production begins and CDK2 is reactivated
DNA replication can occur
"Master switch" at R checkpoint
Turns on last genes needed for the start of replication
TF that blocks progression through the cell cycle
Initiates DNA repair if replication isn't going well
Initiates apoptosis if damage is too severe
p27 inhibits CDK2
p27 is phosphorylated, tagged with ubiquitin
p27 is degraded by the cell
Throughout the cell cycle and the completion of M phase, what has happened to E2F and Rb?
E2F has been degraded
Rb persists in a hyperphosphorylated state
CDK inhibitors (2 families)
INK4 family - block CDK 4/6 complexes
Cip/kip family - block the remaining CDK complexes
Most important inhibitors of the cip/kip family
p57, p27, p21
What do ink4 inhibitor signals promote/inhibit during the cell cycle?
Inhibits phosphorylation of Rb by CDK 4/6
What do cip/kip inhibitor signals promote/inhibit during the cell cycle?
Contact inhibition - p27 on cyclin E
DNA damage/apoptotic factors - p53
p53 inhibits p21 which inhibits CDK2
What is happening in terms of cyclin concentrations and CDK activation during G2?
Cyclin B levels rise and peak at metaphase.
Cyclin B can bind to CDK1 but this isn't enough to activate it.
Summarize the events that occur at the start of the G2/M checkpoint.
To keep mitosis from starting before DNA replication is done:
1. Kinases phosphorylate CDK1 to inactivate it.
2. When replication is done, a phosphatase removes a phosphate from CDK1 to activate it.
What is the phosphatase activated by?
Initially activated by stress or DNA damage through phosphorylation
Is then activated by CDK1/cyclin B complex in positive feedback loop
How do CDK1/cyclin B promote the events of mitosis?
1. Phosphorylation of nuclear lamins
-Destabilizes nuclear envelope
2. Phosphorylation of condensin
-Condensin binds to chromosome, causes supercoiling
3. Phosphorylation of MAPs
-Depolymerization of microtubules, triggers organization of mitotic spindle
What is happening in the cell at the end of the G2/M checkpoint?
When the chromosomes are lined up:
1. CDK1 activates APC
2. APC destroys anaphase inhibitor and cyclin B
Lets anaphase begin, inactivates CDK1
How does DNA damage activate p53 and what are the consequences?
DNA damage elevates p53
Inhibits CDK2 via p21
DNA synthesis stops OR cell apoptoses
List the events that occur at the DNA repair checkpoint.
1. DNA damage occurs
2. ATM/ATR and Chk1/Chk2 activate
3. They stabilize, phosphorylate and activate p53
4. p53 upregulates p21
5. Inhibits CDK2
6. Blocks Rb phosphorylation
7. DNA synthesis is stopped until DNA repair is complete
Describe the structure of p53 and how mutations affect it.
Homotetrameric transcription factor
A single allele mutation will result in a dominant negative effect where the protein loses its functionality
Familial cancer susceptibility due to mutant p53 germ line alleles
MDM2 and stability/regulation of p53
Stability is controlled by polyubiquitin-mediated degradation by proteosome.
MDM2 - ubiquitin ligase which regulates p53 stability; its phosphorylation causes ubiquitination and degradation of p53. Ligase activity inactivated by ATM.
Oncoproteins and how they control MDM2
c-Myc, Ras, viral E1A
Upregulate ARF production
Sequesters MDM2 to nucleus where it can't do anything
THIS SET IS OFTEN IN FOLDERS WITH...
Amino Acid Anabolism
Lymphatic System Histology
Carbohydrate Metabolism 2
YOU MIGHT ALSO LIKE...
Cell Biology: Cell Cycle Checkpoints, Cyclins and…
Molec Cell Bio T4: Cycle
OTHER SETS BY THIS CREATOR
Cardiovascular Pharmacology: Antiarrhythmics
Cardiovascular Pharmacology: Hypolipidemic drugs
Cardiovascular Pharmacology: Anginal Therapy