Cell replication Flashcards
Different division rates of cells
Embryonic vs adult cells (early frog embryo cells - 30min)
Yeast cells (1.5-3)
Necessity for renewal (intestinal epithelial cells - 20h, hepatocytes 1 yr)
What is the quiescent phase
Go -
What are the characteristics of cells going past the checkpoints
Based on nutreints
Growth factors
Why might the cell cycle pause
Undergoes DNA repair
Undergo apoptosis
How do cells leave Go
Reponse to extracellular factors
Tyrosine receptors
Signal amplification
Signal integration/ modulation by other pathways
Ras/Raf/MEK/ERK
What is the role of c-Myc
Growth factor Induces the expression of c-Myc
Promotes Go to G1
c-Myc is an oncogene
What are cyclin dependent kinases
Phosphorylation and dephosphorylation
Forms serine/threonine/tyrosine
Present in proliferating ecll sbut only activate when a cyclin is bound
Why is cyclin called cyclin
Production and degradation cyclic pattern
How are c-myx and cyclin relates
Growth factor induce C-Myc
C-Myc induces expression of Cyclin D
Cyclin D binds to Cdk 4
What are protein kinase cascades
One kinase phosphorylates another kinase which phosphorylates another kinase
Leads to: signal amplification, diversification, opportunity for regulation
Phosphorylation and dephosphorylation controls
How are the cyclin-dependent kinases regulated
Interaction with cyclins
Phosphorylation
What are examples of cyclins
How are cyclins expressed
Transiently expressed at specific points in the cell cycle
Regulated at level of expression
Synthesised then degraded
Stages of phosphorylation and desphosphorylation
Cyclin bindes to cdk
Protein kinases phosphorylate complex
Activating protein phosphatase removes inhibitory phosphate - becomes active cyclin-cdk complex
Positive feedback of cell cycle
Progression induction of Cdks through the cell cycle
What is ubiquitylation of cyclin
Ubiquitin molecules stick onto cyclin
Cell machinery proteasome
How do you regulate cyclins in the cell cycle
Cdks become active and stimulate synthesis of genes required for next pahse eg. cyclinD stimulates cyclin E
Gives direction and timing
Susceptible to degradation
What is retinoblastoma
Molecular brake
Problem when retinoblastoma protein is missing or inactive
Tumour suppressor
Abundant in all nucleated cells
Growth factor (mitogen signalling)
Drives cell proliferation
What does Rb do
Acts as a brake on cell proliferation
Active RB portein binds to inactivated transcription regulated (E2F family)
E2F family turn on DNA polymerase and thymidine kinase - things needed for S phase
How is the Rb activated
Phosphorylation by activation of intracellular signaling leads to the production of G1/S-Cdk complexes
How do E2F members regulate expression
What does p53 do
Arrests cells with damaged DNA in G1
Recognise breaks and activated portein kinases that phosphorylate p53, stabilizing and activating it
