CELL CYLE Flashcards
what are the control proteins?
Cyclin dependant kinases (CDK) + cyclins
what is the purpose of the control system?
ensures the cell cycle occurs in the right order
what affects the checkpoints of the cell cycle?
cyclin/CDK levels due to CDK ability to phosphorylate protein
whar are cyclin dependant kinases?
protein kinases that are characterized by needing a cyclin sub unit bound for enzyme activity, its important in cell division and transcription
what are proline- directed serine/threonine kinases?
A subclass of protein serine-threonine kinases that phosphorylate proteins on a SERINE or THREONINE residue that is immediately preceding a PROLINE residue.
why is kinase dependent on cyclin?
it has a low activity so its needs a cyclin binding partner which leads to a confirmational change
can cdk be phosphorylated alone?
yes and this can be ingibitory or activate kinase
where CDK mostly active?
in the nucleus
what can expression be induced by?
growth factors , multiple signalling athways through control of CDK4 nd CDK6
What is the G0 in the cell cyle?
G0 is when the cell steps out of the cell cycle in G0 it has normal cellular behaviour but is not ready to divide
what drives cyclin expression?
oncogene activation
what drives the cell through different phases of cell cycle?
programmed phosporylation
what causes positive phosphorylation?(activity)
phosphorylation at the C terminus threonine by CAK
what causes negative phosphorylation (inhibtion) and what removes it?
phosphorylation at the N terminus threonine and tyrosine CDC25 phosphotases removes inhibitory phosphates
what happens in G1 to S phase progression?
D1,2,3 cyclins +CDK4,6 commit cell to DNA replication and mitotic division
cycliN E + CDK2 is a critical initiator of DNA resplication when the chromosome unwinding
G1-S progression
phosphorylation of RB stimulates E2F
Accumulation of FOXM1
G1-S progression(DNA replication)
hyperphosphorylation of RB
centresome duplication
induction of histoire synthesis
phosphorylation of replication facters
describe the G1-M process
nuclear envelope breakdown , mitotic condensation and spindle assembly
whta happens during S/G2 phase
cyclin A(A1.A\0 + CDK2, phosphorylate DP1 inactivationg it
what happens during M phase?
cyclin B(B1/B2) + CDK1(aka CDC2)
directs nearly all proccess during mitosis including chromsome condensation and segregation, promtoes assembley of mitotic spindle and degradation of cyclin B essential for exit of M phase.
what ends s phase?
phosphorylation of DP1
what initiates m phase?
CDK1
how is m phase mediated?
CHK and WEE1 mediate dna replication and M phase frim CDK1 activity
apart from cyclin what else can activate CDK’s
Karposi sarcoma virus which inactivates pRB inhibiting cell cycle profression
what cyclin/CDK alterations affect cancer? (CYCLIN D1)
amplification of cyclin D1 causes breast carcinomas and leukamias
hyperactivity of promter due to mitogenic pathways causes diverse tumours
reduced degradatiob due to depressed activity of GSK3
what cyclin/CDK alterations affect cancer? (CYCLIN E & CDK4 )
cyclin E overexpression causes breast carcinoma and defective degradation due to loss of hCDC4 causes breast ,endometrial and ovarian carcinomas
structural mutation of CDK4 causes melanoma
amplification of CDK4 causes several types of cancer
what do CDK inhibitors do?
checkpoints are not passed inappropriately
what are the CDKI and what do they inhibit?
INK4 proteins - nhibitors of CDK4)
- inhibit CDK4/6
Cip/Kip proteins - inhibit all other cyclin-CDK complexes
what is TGFb?
TGFb is growth inhibitory by inducing p15INK4B
what inhibits CKI’s?
Mitogens
