Chapter 21 - Regulation Of The Cell Cycle Flashcards
Cell cycle mediators are?
Cyclins or CDK’s
What are the different cyclins for phases of cell growth?
- Cyclins D : Regulate G1 through the restriction point
- Cyclins E and A : proceed the cell through S phase
- Cyclins B and A : Mitotic cyclins
How does the CDK-cyclin complex work?
- the complex stimulates the kinase activity of CDK
- CDK becomes phsophorylated and this active cyclin-CDK complex catalyzes the phosphorylation of serine and threonine aa residues
- the result is the change in state of substrate proteins which acauses the cell to progress towards the next phase
Cell that temporarily or reversibly stop dividing are?
Quiescence cells
What are senescent cells?
Cells that permanently stop dividibg, eith due to age or due to accumulated DNA damage
Cyclins and CDK’s for different cell phases?
CDK4/CDK6 + Cyclin D -> progression past the “restriction point” at the G1/S boundary
CDK2 + Cyclin E/A -> initiation of DNA synthesis in early S phase
CDK1 + Cyclin B -> transition from G2 to M
Tumor supressor proteins?
Proteins that normally function to halt the cell cycle progression within G1 phase
Neoplastic tissue = ?
Cancerous tissue
Antimetabolites are:
Compounds structurally related to normal cellular compounds
Antimetabolites function;
- Inhibit S phase cells
- their mechanism of action involves inhibition of synthesis of PURINE and PYRIMIDINE nucleotide precusors
- They can also fompete with nucleotides in DNA and RNA synthesis
Give 2 examples of antimetabolite drug:
- Methotrexate
- 5-fluorouracil
Anticancer metabolites
May cause accumulation of G2 phase cells or act without regard to cell cycle phase
Give example on anticancer antibiotic
Bleomycin - result in the accumulation of cells in the G2 phase
Anticancer antibiotcs function;
Their mechanism of action involves interacting with DNA and disrupting DNA function
What agents is often used to treat solid tumors with low growth fractions
Anticancer antibiotics
Mitotic spindle poisons
- Disrupt spindle formation and affect cells in mitosis
-
What if retinoblastoma protein (RB) ?
Tumor supressor protein that functions to halt the cell cycle in resting or G1 phase.
In resting cells, it has less phosphorylated aa residues
In active cycling cells, it is hyper phosphorylated as a result of growth factor stimulation and signaling via MAP kinase.
How does RB work in resting cells?
It contains few aa phosphorylated residues, so it prevents entry of cell into S phase by binding to TRANSCRIPTION FACTOR E2F + binding partner DP1/2 .
Note: transcription factor E2F and binding partner DP1/2 are critical for cell to process to the S phase.
How does RB work in actively cycling cells?
- RB progressively is hyperphosphorylated as a result of MAP kinase activity as a result of which D-CDK4/6 complexes are activated and they phosphorylate RB.
- further phoshprylation of RB by E-CDK2 allows the cell to move out of G1
- this hyperphosphorylated RB can not inhibit transcription factor E2F and its partner DP1/2 as a result of which they bind to DNA
- binding of E2F to DNA = activated genes whose products are imp for S phase.
Examples of EF2 regulated genes ?
Thymidine kinase and DNA polymerase
What is p53?
A tumor supressor protein that plays major role in G1. This protein activates and phosphorylates as a result of nuclear DNA damage and produces p21 to halt cell cycle progression.
What cyclin dependent kinase inhibitors inhibit Cyclin D?
INK4
What are potent inhibitors of CDK2 kinases?
CIP/KIP
note: p21 is a member of CIP/KIP family
CDK1 is phosphorylated on?
Tyrosine residues
