CANCER- cell cycle Flashcards
what is over expressed in many tumours?
the c-Myc oncogene
what are the key components of signalling pathways?
- Regulation of enzyme activity by protein phosphorylation (kinases)
- Adapter proteins
- Regulation by GTP-binding proteins
what do adaptor proteins do?
molecules that influence signal transduction pathways and scaffold together proteins
what is Ras
ras- major oncogene
member of GTPase
ras becomes activated when bound to GTP
what may increase risk of tumours in reference to ras?
mutations that either prevent GAP binding, or prevent GTP hydrolysis will increase the amount of active GTP-loaded Ras
what does ras activate? and what does that lead to?
it activates an Extracellular signal-regulated kinase cascade (ERK)
ERK then goes on to stimulate changes in
cell proteins and gene expression (eg c-Myc) to promote cell division
what is a key regulator of the cell cycle?
cyclin-dependent kinases (Cdks)
Present in proliferating cells throughout cell cycle
the activity is regulated by interaction with cyclins
they are phosphorylated very quickly
what are cyclins?
Transiently expressed at specific points in the cell cycle and are activated by cdks
what cdks control S phase, G1 and M phases?
S- s-cdk, binds to cyclin A
G1- G1/S-cdk, binds to cyclin E
M- M-cdk, binds to cyclin B
what oncogene is overexpressed in 50% of breast cancers?
cyclin D1
what so cyclin kinases do?
phosphorylate proteins which drive cell cycle progression
if the cyclin kinase-cyclin complex from the stage before has not been made and degraded, releasing a transcription factor, then the next complex wont form and the cell cycle will stop
what are cdks regulated by?
cdk inhibitors.
bind to cdks, hold onto the cdk kinase-cdk complex and inactivate it
cdkIs are important in cancer treatment
what are the two CKI families?
INK4 family - inhibit Cdk4/6, and displace the cyclin D therefore arresting G1
CIP/KIP family- inhibit all cdks, no displacement of cyclin, complex just held together and kept inactive
