Cell determination and cell senescence Flashcards
Positive feedback mechanism
- Signal causes A to be made or activated
- A causes B to be made or activated
- B causes A to be made or activated
- Once the signal stops the cycle keeps going
Melanocyte differentiation
- MSH-MC1R signalling causes cAMP to be made
- cAMP causes MITF to be made via CREB activation
- MITF causes cAMP to be made via MC1R transcription due to basal activity
What are master gene regulators in skeletal muscle differentiation
Myogenic factors; MYOD1, MYF5, MYOG and MRF4
What are E proteins
Widely expressed transcription factors that work as dimers with myogenic factors
what is ID1
A protein in myoblasts that strongly binds to E proteins but not DNA, therefore acting as inhibitors to differentiation
What happens to activate the muscle-specific gene
MYOD1 and E protein form a dimer that can bind to the gene promoter of DNA
How is differentiation inhibited in myoblasts
ID1 and E proteins bind forming a dimer that cannot bind to the DNA promoter, therefore preventing the activation of that gene, preventing differentiation
Cell senescence define
Permanent cell growth arrest following extended cell proliferation
What are the morphological changes that occur in senescent human fibroblasts
The edge of the cells are hard to see due to loss of lamins
Prominent nucleoli
Large flat cells
What are the molecular markers present in senescent cells
Many lysosomal beta-galactosidase
Lots of protein p16 since its a cell-cycle inhibitor
What is a telomere
1000’s of repeats of a hexamer sequence (TTAGGG) at chromosome ends that protects the chromosome from DNA damage and prevents chromosomes from fusing with other chromosomes
What is telomerase and what is it required for
An RNA-dependant DNA polymerase
It maintains the telomere length
What is the structure of telomerase
An RNA-protein complex, made of TERC and TERT.
TERT
telomerase reverse transcriptase, the protein part
TERC
telomerase RNA component, the RNA part
Why do human somatic cell chromosomes shorten
TERT is not expressed
Why are germline cells and cancer cells immortal
TERT is expressed so chromosomes maintain full length telomeres
Telomere shortening cell senescence pathway
- Telomere shortening leads to DNA damage signalling
- Tumour suppressor p53 gene expressed
- Growth inhibitor p21 is made which inhibits CDK1 and CDK2
- Cell cycle is arrested in G1 phase
Radiation/DNA damage cell senescence pathway
- DNA damage causes p16 to be expressed
- p16 binds to CDK4 and CDK6 therefore cyclin D cannot form an active complex
- pRB isnt phosphorylated so remains bound to E2F
- E2F cannot promote the transcription of proteins required for the progression of the cell cycle
- Cell cycle arrests in the G1 phase
How do advanced cancer cells bypass cell senescence
They express TERT, and have p53 and p16 defects. This means the cell cycle wont be arrested so there will be rapid, uncontrolled divisions forming tumours
How is cell senescence and ageing linked
Telomere length decreases in ageing tissues causing p16 to be expressed
What is a master gene regulator
A master gene regulator is a transcription factor that co-ordinately regulates many/all of the specialised genes expressed by a particular cell type. It may not only positively regulate many genes but can also co-ordinately negatively regulate others.
What is a master gene regulator in melanocytes
MITF
