Lecture 22 Flashcards
What is a CDK? What other protein is required to bind to it for activity?
Cyclin-dependent kinase (CDK) is a protein complex that binds to cyclin to phosphorylate other proteins.
How many CDKs and cyclins do animals have?
Animals have 8 CDKs and 10 cyclins.
True or False: The abundance of CDK proteins cycles with the cell cycle, while the abundance of cyclin proteins is stable.
FALSE: the abundance of cyclin varies while the abundance of CDK proteins remains stable.
True or false: The activity of CDKs cycles with the cell cycle.
TRUE
What is the T‐loop, and what does it do during regulation of CDK activity?
The T-loop is a structure that contains Thr160 within CDK that normally blocks the ATP binding cleft when CDK is not phosphorylated.
What reversible protein modification (and on what aa) is required to activate CDK, andwhat reversible protein modification (and on what aa) then inactivates it?
The phosphorylation of Tyr15 inactivates CDK while the phosphorylation of Thr160 and the removal of Tyr15 activates CDK.
What is the importance of the Destruction box? What recognises this sequence and what happens when it binds it?
The destruction box is a 9 amino sequence at the N-terminus of a protein. DBRP (destruction box recognising protein) is the protein that recognises this sequence and ubiquitin which acts as markers for degradation by proteasomes.
List the four mechanisms that regulate CDK/cyclin activity.
The four are:
- Phosphorylation of CDK
- Controlled degradation of cyclin
- Regulated synthesis of CDK and cyclin
- Protein inhibitors of CDK activity
Does the binding of p21 activate or inhibit the activity of CDK?
Inhibits the activity of CDK
Give three examples of target proteins of CDKs. For all three, which phase of the cell cycle is it phosphorylated, and what happens when it is phosphorylated?
The three are nuclear lamins, condensins and retinoblastoma (Rb). Nuclear lamins are phosphorylated in prophase (cause breakdown of nuclear membrane). Condensins are phosphorylated in interphase (organises chromosomes). The phosphorylation of retinoblastoma occurs at checkpoint G1/S-CDK which activates enzyme for DNA synthesis (E2F).
What is the role of the protein Rb1?
Protein Rb1 negatively regulates the proliferation of cells.
What is a checkpoint? Give several examples.
A checkpoint is a point in the cell cycle where the progression of the cell into the next stage of the cycle can be stopped due to damage of DNA or signal to stop. (e.g. liver cells/skin cells- exit and reenter cell cycle when needed, DNA damage - need to be fixed before continuing)
What is the mechanism by which a double stranded break causes a cell cycle arrest? How is this arrest relived once the break is repaired?
The double strand break causes the pRb to bind to E2F (pRb-E2F blocking mechanism) inducing cell cycle arrest in G1. E2F become inactive and is unable to promote transcription of genes necessary for DNA synthesis (S phase) which commits the cell to mitosis and cell division. Once the break is fixed, CDK phosphorylates pRb which activates E2F so that cell can continue into S phase.
What is Knudson’s two‐hit hypothesis? How does this explain the formation of tumours in the retinas of people with Rb?
Knudson’s two-hit hypothesis suggests that cancer is a result of the accumulation of mutation on DNA. A mutation to the DNA of both genes (Rb) causes the loss of function which results in the formation of tumours.
What is a tumour suppressor gene and what is an oncogene?
A tumour suppressor genes are genes that code for cell proliferation (ex: Rb1). Oncogene are genes that can prevent other cells from undergoing apoptosis and signals for ongoing proliferation when activated. (potentially cancer causing)
