Cell Cycle Regulation And Disruption Flashcards
What is cell division control provided by?
CDKs - cyclin dependent kinases
Cyclins - kinase regulatory proteins
What does uncontrolled cell division result in?
Cancer
What happens if the cell cycle is not initiated by external sequences?
They enter into a prolonged G1(G0) due to lack of G1 cyclins which are destroyed during mitosis
What cyclins and CDK make up the complex G1-Cdk?
Cyclin D1, D2 and D3
Cdk4, Cdk6
What cyclins and CDK make up the complex G1S-Cdk?
Cyclin E
Cdk2
What cyclins and CDK make up the complex S-Cdk?
Cyclin A (SPF) Cdk2
What cyclins and CDK make up the complex M-Cdk?
Cyclin B (MPF) Cdk1
How are Cdk/cyclin complexes regulated?
Cyclic proteolysis
Transcriptional regulation
Inhibitor proteins (CKIs)
Covalent modification (phosphorylation/dephosphorylation)
What challenges are present in each cell division?
Must not replicated damaged DNA
Must replicate one, and only one, complete copy of the genome
Must properly segregate a complete copy to each daughter cell
What happens at the G1/S checkpoint?
DNA damage assessment
What happens at the mid S checkpoint?
DNA replication checkpoint I
What happens at the G2/M checkpoint?
DNA replication checkpoint II
What happens at the M checkpoint?
Spindle assembly checkpoint
What happens at the post M checkpoint?
Polyploidy checkpoint
What happens if there is a problem with the polyploidy checkpoint?
Leads to tetraploidization
What happens if there are problems at the DNA replication checkpoint?
Leads to telomere dysfunction, rearrangements and amplifications
What do tumor suppressors do when they find irreparable damage to DNA?
Send into programmed cell death
What are the best described tumor suppressors?
p53 and pRb; both of which are transcription regulators
What is p53 considered and why?
It is considered the guardian of the genome because it halts the cell cycle in response to DNA damage thus allowing time for repair
What are some genes that p53 regulates?
p21: mitotic arrest
GADD45: DNA repair protein
What happens when p53 becomes mutated?
Converts from a tumor suppressor to an oncogene.
Associated with ~50% of all tumors when mutated
When is p53 activated/phosphorylated?
In response to DNA damage
When is pRb inactivated/phosphorylated?
In response to cdk2 resulting in released E2F that can bind DNA and regulate expression of cell division genes
What happens in M phase following G2?
Prophase Prometaphase Metaphase Anaphase Telophase
What happens in prophase?
Chromosomes condense; nucleoli disappear, mitotic spindle forms
What happens in prometaphase?
Nuclear membrane breaks down; chromosomes attach to spindle
What happens in metaphase?
Chromosomes maximally contracted and arranged at equatorial plane
What happens in anaphase?
Centromeres split and sister chromatids separate to opposite poles
What happens in telophase?
Chromosomes decondense, nuclear membrane reforms, cytokinesis
What is required in metaphase to anaphase transition?
M-Cdk inactivation required.
What is required from prophase to metaphase?
Active m-Cdk
What are the targets of M-Cdk?
Condensins
Laminin
What are Condensins?
Proteins involved in chromosome condensation
What does phosphorylation of laminin cause?
Causes it to depolymerize, resulting in nuclear envelope breakdown
What does APC affect?
Securin
Separase
Cohesins
What is securin and what is one of its functions?
Separase inhibitor
It initiates anaphase (APC target)
What is separase?
A protease that targets cohesion to allow sister chromatid separation
What is involved in programmed cell death?
Removal of factors
Extracellular signals
Cell damage
What are oncogenes?
Mutated forms of normal proteins (proto-oncogenes) involved in control of cell growth
How can viruses become tumor causing?
1) virus inserts into host genome
2) when excised May take a cope of genome with it
3) mutates the genome
4) reinfect and inserts mutated gene into new host
What are some known oncogenes?
Mutant G proteins and tyr-kinases?
What does erbB encode?
EGF receptor lacking EGF binding domain
What does sis encode?
Mutant PDGF receptor
What does ras encode?
A G protein with no intrinsic GTPase activity
What does myc encode?
A transcription factor that regulates proliferative proteins
What is different about the ErbB protein?
Tyrosine kinase is constantly active
What is HPV highly associated with?
Cervical cancer
What do the early HPV proteins (E6 & E7) do?
They bind and inactivate p53 and pRb the tumor suppressing proteins
What else does HPV E6 do?
Targets Bcl2 which helps maintain a cell that should undergo apoptosis
