Growth And Division Of Cell Flashcards
3 roles of Mitogenic and growth factors
- Stimulate cell division (eg. Hormones (Oestrogen), cytokines/growth factors(EGF))
- Stimulate protein synthesis (eg. mTOR pathway)
- Survival factors prevent apoptosis (maintain the balance between cell death and cell division)
What are the regulatory progress involved in cell growth and cell cycle regulation?
- Cell cycle progression
- Cell cycle checkpoints
- Role of tumour suppressors
- cdc25c phosphate-CDK 1 regulation
What are the regulators of cell cycle progression?
[Cyclins, Cyclin-dependent kinases (CDKs)]—> forms Cyclin-CDKs Complex
Cyclin-dependent kinase inhibitors (CDKi)
Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells.
What are the extracellular factors that regulate cell growth and proliferation?
- Mitogenic
- Growth factors (EGF, BFGF, BDGF)
- Extracellular matrix (cell-cell/ cell-matrix contact)
- Ions such as Ca2+
What are the cyclin and kinase involved in
Function: Progression past the restriction point at the G1/S boundary
Cyclin: D
Kinase: CDK4, CDK6
What are the cyclin and kinase involved in
Function: Inhibition of DNA synthesis in early S phase
Cyclin: E,A
Kinase: CDK2
What are the cyclin and kinase involved in
Function: Transition from G2 to M
Cyclin: B
Kinase: CDK1
What are the 3 checkpoints that are being regulated at cell cycle?
G1 (Restriction) Checkpoint
G2/M checkpoint
M (spindle/ metaphase-anaphase) checkpoint
What is checked during
G1( Restriction checkpoint)
Integrity of DNA and other external factors
Influenced by Growth factors Nutrients Cell size DNA damage
What is checked during
G2 (G2/M) checkpoint
Completely replicated chromosome and DNA damage
Influenced by
Cell size
DNA damage
DNA replication
What is checked during
M (spindle/ Metaphase-Anaphase) checkpoint
Ensure all sister chromatids are correctly attached to the spindle microtubules before cell enters the irreversible anaphase stage
Influenced by
Chromosome attachments to spindle
What protein is involved in checkpoint regulation?
Retinoblastoma Protein (RB protein) -Tumour suppressor function in resting or G1 phase of the cell cycle
How does RB protein regulate cell cycle in
Resting cells
Partially phosphorylated Retinoblastoma (RB) protein, which prevents entry into S-phase by binding to transcription factor E2F & its binding partner DP1/2 (critical for G1/S transition)
How does RB protein regulate cell cycle in
Actively cycling cell
Progressive hyperphosphorylation of Retinoblastoma (RB) protein, which is achieved by
I)Growth factor signaling
II) Activation of Cyclin D-CDK4/6
III) Cyclin E-CDK2
CDK4/6 can be inhibited by p16 (CDKi)
If RB protein is hyperphosphorylated during G1 phase, what will happen?
Hyperphosphorylated RB protein will dissociates from E2F and cell moves out of G1