Ch 9 Lecture (Replication) Flashcards
replication is confined to the … phase
S phase
the G1-S checkpoint is also known as the
restriction point
start
in order to pass through the start checkpoint, the cell must
have a certain minimum amount of growth and have no DNA damage
four steps of checkpoint passage
- Cell must express the correct growth factor receptor
- Cell must have growth factor present to bind to the receptor
- Cell must receive continued growth factor signal long enough to trigger the production of active cyclin proteins
- Cyclin proteins must activate a set of enzymes called cyclin-dependent kinases
signal from cell membrane receptor to the nucleus is mediated by
signal transduction pathways
components of signal pathways are also called
proto-oncogenes
Cell must receive continued growth factor signal long enough to trigger the production of
active cyclin proteins
Cdk
cyclin-dependent kinases
tumor suppressor genes
Genes whose products prevent the activation of CdK enzymes when criteria have not been met
examples of tumor suppressor genes
Rb and p53
Rb is usually found in an
active, unphosphorylated form
Rb control steps
- With continued growth factor signal, G1-Cdk (Cyclin D-Cdk) activity is stimulated
- Active G1-Cdk will phosphorylate Rb
- Phosphorylated Rb will be inactivated and release the transcription factor E2F
- E2F will activate the transcription of genes required for entry into S phase
- Downstream components participate in positive feedback of E2F
what does p53 do
Prevents passage through checkpoint if DNA damage has occurred
Transcription of p53 is … by growth factor signal in preparation for restriction point decision
upregulated
activity of p53 is under negative regulation by
Mdm2
how does Mdm2 work with p53
Transcription of Mdm2 is upregulated by p53
Binds to p53 and targets it to degradation pathways
Also binds to p53 and inhibits its function as a transcriptional activator
p53 after DNA damage
p53 and Mdm2 are phosphorylated
Mdm dissociates from p53
p53 degradation is decreased
p53 translocates to the nucleus and activates the expression of genes that repress cell cycle progression
Rb and p53 are
negative effectors of cell cycle progression
p21
Expressed as a result of DNA damage and p53 activity
Binds to cyclin/CdK complexes needed for Rb inactivation
order of tumor suppressors
p53-p21
p27
Rb