Flashcards in Mitosis/Cell Cycle Regulation Deck (33)
What are the the two proteins that control cell division
1. Cyclin dependent kinases: phosphorylates things
2. Cyclins: kinase reg proteins
Cell cycle is initiate in response to external signals:
If external factors arent present to stimulate movement into the cell cycle, cells move out of it: G0, they are not replicating. Need Forces that could be hormonal or G1 cyclins
____ is an important transcription factor.
Myc: oncogene that act proteins req for cell cycle reg.
G1 complex is: ____D. G1S cdk in important in cyclin ____. S-Cdk is important in cyclin ____. M-Cdk is important in cyclin ____
cyclin; E; A; B
Growth factors and inflammation upregulate cylin ____
SCF and APC are:
ubiquitin ligases which cause them to be degraded. Want to get rid of cyclins to get from one portion of cyclin to another.
G1S checkpoint is most important check point for cell. The cyclin here is _____:
p53 and rB protein work. Two big suppressor proteins we know of; E
How is cdk/cyclin regulated
1. cyclic proteolysis
2. transcriptional regulation (cyclin D)
3. inhibitor proteins (CKI's)
4. Covalent modification (phosphorylation)
Need cyclin ___ in order to enter into G1
The protein req for ubiquitin ligases are: ____ and APC. The proteins req for TF;s are ___ ___ ___. The tumor supressor proteins are ____ and ____. Proteins req for kinases are ___ and _____. The proteins for phosphatases are _____
SCF; Jun, Fos, Myc, E2F (reg at G1s checkpoint)
p53, pRb; CAK, Wee1; Cdc25
p21 is ____inhibitor
CDK (cyto kinase)
What needs to happen during cell division
1. must not replicate DNA that has been damaged
2. Must replicate only one complete copy of the genome
3. must properly segregate a complete copy to each daughter cell.
What are the 5 critical DNA damage checkpoints
1. G1/S: Dna damage assesment
2. Mid S: DNA replication cp 1
3. G2/M DNA rep cp2
4. M: spindle assembly cp
5. Post M : polyploidy cp (still a single nucleus)
what do tumor suppressors do
proteins which serve as cp's for the cell cycle. monitor for irreparable damage to DNA. Send cells into programmed cell death.
what is the guardian of the genome
1. halts cell cycle in response to DNA damage and allows time for repair. Mutation of p53 converts it from a tumor suppressor to an oncogene...mutant p53 is associated with 50% of all tumors
Which enzmyes does p53 regulate?
1. p21: mitotic arrest
2. GADD45: DNA repair protein
how does p53 work
1, dna damage occuring. p53 gets activated by ATM/ART kinase. STarts transcribing genes one is which p21, which inhibits cdks. pRb is inactivated/phosphortylated in response to cdk2 and inhibts E2F from acting (repressor protein). As long as pRb is not phosphorylated, it binds to E2f and keeps it from going to the nucleus and upregulating all the genes needed for DNA synthesis. If p21 is here pRb stays to E2F (doesnt get phosphorylated) and halts cell cycle completely which is what we want for damaged cells.
If progress through G1/S...systems are in place to ensure that replication will initiate once, at each origin of replication during ____phase. Systems are in place to ensure that replication is complete before initiation of ____ phase. ___ phosphorylates APC, an E3 ubiquitin ligase.
S; M; M-cdk
m-cdk is cyclin ____ complex
M-cdk inactivation required in order to move into _____
M-cdk is required for cells to enter the M phase (mitosis) after G2. What are the phases of mitosis?
1. prophase: chromosomes condense, nucleoli disappear, mitotic spindle forms.
2. prometaphase: nuclear membrane breaks down; chromosomes attach to spindle.
3. metaphase: chromosomes maximally contracted and arrange at equatorial plane
4. anaphase: centromeres split and sister chromatids sep to opp poles.
5. telophase: chromosomes decondense, nuclear membrane reforms, cytokineses
what does M-cdk target
1. Condensins: proteins inv in chromosome condensation
2. Laminin: phosphorylation of laminin causes it to depolymerize, resulting in nuclear env breakdown.
what are APC effects
1. Securin: separase inhibitor; an APC target..initiates anaphase
2. Separase: a protease that targets cohesin to allow sister chromatid sep
3. Cohesins: hold sister chromatids together.
What are APC targets:
cyclin B (which has to disappear in order to enter anaphase)
securin:inhibitor of separase
separase:cleaves cohesin, and allows onset of anaphase
when we end mitosis we have No ____
How needs to happen for programmed cell death
1. removal of factors: loss of mitogenic factors
2. extracellular signals: FasL, TNFalpha, TGFbeta
3. Cell damage: DNA damage, oxidative stress, etc.
what are the proteins involved in programmed cell death
1. death domain receptor: Fas
2. tumor suppressors: pRb, p53
3. mitochondrial proteins: cytochrome c, Bcl2
4. caspases: diassembles cytoskeleton and allows act of other enzymes that breakdown DNA
____form the pore to release cytochrome c
Bcl2; promotes survival
Mutated forms of normal proteins involved in control of cell growth:
oncogenes; some were first identified in tumor causing viruses
what are Gain of function type of mutations
being activated without any ligand bonding. GF receptors are being turned on w/o GF binding.
Mutant ___ proteins and Tyrosine kinases are known _____
What are the proteins involved in oncogenic activity
1. erbB: encodes EGF receptor lacking EGF binding domain
2. sis: encodes a G protein with no intrinsic GTPase activity
3. ras: encodes a G protein with no intrinsic GTPase activity
4. myc: encodes a TF that reg's proliferative proteins.