Cycle Cellulaire Cont: 1 Flashcards
What is the SCF cmplex?
Similar to the APC the SCF is a CDk- degrader
Activates at the end of G1 and S -> G2 → Degradation of Cycline-G1, Cycline-G1/S:
What is the role of the SAC (not APC)?
SAC inhibits the degradation of Cycline M and securing until all kinetochores are aligned
What are the two possible routes of DNA repair activated by ATM
ATR?
histone γH2AX -> DNA repair
p53 → stop the cell cycle
Describe p53,
p53 est normalement continuellement produite et dégradée
phosphorylation will stabilize it (following DNA damage)
when activated, p53 leads to transcription of p21 which inhibits Cdk activity (CKI)
of course block Cdk-G1/S and Cdk-S (because we would detect DNA damage during DNA replication which happens during S phase)
Cdc6 role
Key protein in bidning to origin of DNA replication complex that initiates the replication (ORCS)
Cdc6 is phosphorylated and degraded by Cdk-S
Cdc6 is degraded following that initiation to assure one ORC leads to one single replication per cycle
What are three ways of CDk activity control?
Dégradation
de cycline -> proteasome
Inhibiteur de
cycline/Cdk -> p21
phosphorylation de Cdk -> Wee 1
What is Wee 1 and what does it result in?
Wee 1 is an inhibitory kinase that leads to → inhibition of Cdk-M
Holds the cell in G2 cycle.
What is Cdc25 and what does it result in?
Cdc25 is a Wee 1 antagonist → removes phosphorylation:
Cdc25 removes the phosphore from the Cdk-M
This leads to Cdc25 being phosphorylated
This leads to a positive retro control → more Cdc25 active → more Cdk-M active and so on → transition to G2/M
What is an example of a molecule that leads to cell quiessence?
Rétinoblastome (Rb): and p53
What is a mitogene?
Mitogène = signal qui stimule l’entrée dans le cycle cellulaire
What is the role of Rb and p53 in relation to tumors?
Rb and p53 are Tumor Suppressors:
These are genes that will be mutated (inactivated) in tumors:
p53 is mutated in over 50% of cancers
-> a lot of cell replication without control
What do we mean by: récepteurs sont des proto-oncogènes
It is possible that we get activating mutation:
La cellule active les gènes de la prolifération cellulaire même quand il n’y a pas de mitogène
These are proto-oncogenes that activate the receptor and thus the chain
What is p21?
p53 transcrit le gène de p21 qui est un
inhibiteur de Cdk (CKI)
Given a cell with high DNA damage, what molecule do you expect to see? What does this mean for the cell?
un autre inhibiteur plus fort, p16
cycle cellulaire devient arrêté de façon
irréversible: -> sénescence cellulaire
What is sénéscence cellulaire?
Mécanisme d’arrêt irréversible du cycle cellulaire
