Graeme Finlay 7 Flashcards
What is the difference between oncosis and apoptosis?
Oncosis is passive cell death often following severe injury while apoptosis is cell death brought about by an active, physiological process
How does apoptosis normally function?
In development where it can form vital structures such as the hollow blastocyst and remove unwanted structures such as webbing between digits
Throughout the life of the organism where it regulates cell turnover and removes unwanted cells
What are the various physiological and pathological stimuli that can induce apoptosis>
Activation of death receptors involved in the elimination of abnormal cells
Removal of survival factors such as growth factors
Presence of apoptosis inducing growth factors or hormones
Loss of normal epithelial cell-cell adhesion
DNA damage, cell cycle deregulation, viral infection, oxidative stress and hypoxia
How is apoptosis regulated?
By the cell death abnormal (ced) genes including ced3, ced 4, ced 9 and EGL-1
What is ced 3?
It is a cysteine protease which cleaves specifically after aspartic acid residues
What is the function of ced 4?
It is an activator of ced 3 protein
What is the function of ced 9?
It is an inhibitor of ced 4 and therefore an inihibitor of apoptosis
What is the function of EGL-1?
It is an inhibitor of ced 9 and therefore a promoter of apoptosis
What are the mammalian homologs of the ced genes from C. Elegans?
13 homologes have been identified known as caspases and stored as zymogens until induced to oligemerize or autocatalytically cleave to P2010 oligomers which cleave key cellular proteins
Gelsolin which causes cytoplasmic blebbing by deregulating actin fibre breakdown,
Nuclear lamin which causes chromatin condensation and nuclear fragmentation poly(ADP-ribose) polymerase which leads to a suppression of DNA repair
An inhibitior of a DNAse which leads to intrnucleosomal DNA cleavage
What is the oncogene involved in causing low-grade B cell lymphoma with a translocation at t(14:18)
BCL-2 which becomes translocated into the IgH locus and overexpressed. This oncogene does not stimulate proliferation but promotes cell survival in a quiescent state and is homologous to ced 9 of C. Elegans
What are the different domains in the BCL-2 protein?
BH4 which has anti-apoptotic activity and BH3 which has proapoptotic activity and acts as an amphipathic ligand domain. The C-terminal hydrophobic transmembrane domain allows the protiens to localise to the outer mitochondrial membrane, ER and Nuclear membrane. They control the release of pro-apoptotic stored in the mitochondria
What BCL-2 proteins are functional analogues of the EGL-1 of C. Elegans?
Those which only contain the BH3 domain
How does altered expression of the Bcl-2 family cause resistance to apoptosis in cancer?
The ratio of pro and anti-apoptotic species controls cell fate. A truncated EGFR increases malignant character by up regulation of Bcl-XL. The tumour suppressor genes BAX and Bak are deleted and Bcl-2 is often increased in expression giving resistance to apoptotsis.
How can the altered expression of the Bcl-2 family in cancer cells be combatted?
anti inflammatory drugs can induce apoptosis by decreasing Bcl-XL expression
What is the link between apoptosis and metastasis?
Apoptosis may be the rate-limiting step for metastasis