Cell cycle regulation Flashcards
What are the 4 (5) stages of the cell cycle
(G0), G1, S-phase, G2, M-phase
What protein is the most important control of the cell cycle
Cdk’s (and cyclins)
What classes of Cyclins are there and when are they active?
- G1/S-cyclins: Activate Cdk in late G1. They help trigger progression through start, resulting start of the cell cycle. Their levels fall in S phase
- S-cylin: Bind to Cdks soon after progression through Start and help stimulate chromosome dumplication. S-cyclin levels remain high until Mitosis, and these cyclins also help with control of some early mitotic events
- M-cyclins: Activate Cdks that stimulate entry into mitosis after G2. M-cyclin levels drops mid-mitosis
Are Cdks active when Cyclins are absence?
NO
How do Cdks gets activated due to cyclins?
Absence of cyclins: active site of Cdks is partly obscured by protein loop (T-loop). Cyclin binding causes the T loop to move away from active site. This partly activates the Cdk protein. For fully activation of Cdk: Cdk activating kinase (CAK) needs to phosphorylates an amino acind near the entrance of the Cdk active site
What is an example of Cdk inhibitor protein (CKI’s)
P27
Where does APC/C stand for and when is it involved?
APC/C= anaphase promoting complex). After M-cyclin has triggered the complex processes leading up to metaphase –> climax with the separation of sister chromatids. Although M-cdk activity leads to this, APC/C throws the switch that initiates sister chromatids separation by uniquiltylating proteins and thereby triggering their destruction. APC/C targets the inhibitory protein Securin for destruction. They also targets S+M cyclins for destruction, leading to the loss of most Cdk activity in anaphase
What happens after Erf enters the nucleus to S-cdk activation?
Erf enters the nucleus, this will help with the production of transcription regulatory proteins like Myc. Myc promotes cell cycle entree. When Myc is expressed: a delayed response gene expression which will lead to activation of G1-Cdk. In order to trigger cell cycle start, the E2F protein needs to be active. It’s IA when the active Rb protein is binded to it. G1cdk inactivates Rb which will lead to active E2F. E2F will help with S phase gene transcription (G1/S cyclin and S-cyclin). This all has a positive feedback on activating E2F proteins. Eventually this will lead to the cell going to S phase
What will happen when Rb gets mutated and stays inactive
E2F will always be active which will lead to hyperproliferation
What is the function of Arf?
Arf is a protein involved in regulation of the cell cycle (G1). It can prevent cells from entering S phase. Arf is also involved in activating P53.
Can P53 inhibit the activity of Cdk?
Yes and no. It can help with the expression of Cds inhibition proteins.
How is Arf involved in activating P53?
P53 is inactive when Mdm2 is bind to it, which will also lead to de degradation of P53 when bound for a long time. Arf can help removing Mdm2 (it can bind Mdm2 to itself), so P53 can be active.
What can the Adenovirus do to promote tumor growth?
Adenovirus has a protein what looks like E2F aka the E1A. E1A binds to a Rb and acts like E2F. Every cell will go into S-phase. Also, Adenovirus has a protein what can bind to P53 to prevent apoptosis: E1b
