Kinases 1 Flashcards
G1
commitment to cell division
S phase
DNA synthesis replicate genome
G2
cell mass doubled
M phase
cell division - mitosis and cytokinesis
CDKs are only activated when
bound to cyclins
does the concentration of cyclins or CDKs oscillate during the cell cycle
the conc. of CDKs stays the same
the conc. of cyclins oscilates
APC/C
member of the ubiquitin ligase family - proteolytic destruction
ubiquitabtion of securing and S+M cyclins
Anaphase promoting complex
Paul Nurse and Tim Hunt
PN - fission yeast - CDKs
TH - discovered cyclins in sea urchins
WEE1
Kinase which is a negative regulator of cell division
Kinase
an enzyme which catalyses the addition of phosphate onto substrate
Phosphotase
dephosphorylates
CDC25
positive cell division regulator
when wee1 phosphorylates CDK 1 what happens
CDK 1 remains inactive
when cyclin B is bound to CDK 1 and cdc25 is present
cdc25 dephosphorylates the complex making it active and so the cell cycle progresses from G2 –> M
in s.pombe cdc2 is a
CDK1
in s.pombe cdc13 is a
cyclin B
Cdc2 is important as
it is a CDK 1 which causes cross from G2 to m
- mitotic spindle formation, cytoskeleton disassembly, Golgi and Er fragmenting, nuclear envelope breaks down
Cdc2 is important as
it is a CDK 1 which causes cross from G2 to m
- mitotic spindle formation, cytoskeleton disassembly, Golgi and Er fragmenting, nuclear envelope breaks down
3 major cell cycle checkpoints
Late G1 - is environment favourable - commit to cell cycle
G2/M checkpoint - Is all DNA replicated? is env favourable? Control system triggers early mitotic events to chromosome alignment in spindle in metaphase
Metaphase anaphase transition - are all chromosomes attached to the spindle
cyclins each cell cycle
undergo cycle of synthesis and degredation
4 classes of cyclins
G1/S cyclins, start, S (chromosome duplication), m Cyclins (stimulate entry into mitosis)
full activation of the CDK-cyclin complex occurs when
CDK activating kinase (CAK) phosphorylates an amino acid near the entrance to CDK active site - conformational change - allowing the CDK to phosphorylate its target properly
CDIs (CDK inhibitory proteins)
regulate cyclin-CDK complex by rearranging the active site and inactivating the CDK
primarily control G1/S and S-CDKs
anaphase metaphase transition
APC/C - mem. ubiquitin ligase family
catalyses the destruction of securing and SandM cyclins
securin
normally protects the protein linkages that hold sister chromatids together in early mitosis - destruction to progress to anaphase
SCF
another ubiquitin ligase
- ubiquilate CDI proteins in late G1, and helps control S-CDK activation
- activity is constant through the cell cycle - controlled by phosphorylation
origin replication complex
late mitosis and early G1
cdc6 and cdt1 bind at ORC and help to load mcm proteins
thought to serve as helices unwinding DNA
Late mitosis early G1 app/c
triggers the destruction of gemini
late G1 - APC/C turned off
gemini accumulates and inhibits Cdt1 formation during S phase onwards
mitosis APC/C complex
triggers the destruction of securin - liberates the protease that cleaves cohesis - initiates the separation of the sister chromatids
M-CDK
drives early mitosis, assembly of the spindle and ensures that the chromatids are attached to opposite poles of the spindle
also triggers the break down of the nuclear envelope, actin cytoskeleton rearrangement
M-CDK activation - accumulation of M cyclin
Wee1 phosphorylates (at 2 neighbouring sites) and holds the complex in an active state until CDC25 comes along and removes the inhibition by being a phosphatase
Mdck positive feedback loop
activation MCDK inhibits Wee1
kinetochore microtubules attach
the plus ends of their microtubules at the kinetochore on centimetre of chromatids
astral microtubules
help to position the spindle
pericentriolar matrix
nucleates an array of microtubules - fast growing plus end outwards
centrism duplication
same time as the cell enters S phase -G1/D-CDK (cyclin E and CDK2) trigger cell cycle entry
M-CDk also changes the microtubule behaviour by phosphorylating 2 proteins that control
MT dynamics
MAPS and MT dependent motor proteins
assembly of the contractile ring depends on
protein proteins - nucleate and assemble parallel array or linear unbranched actin filaments
overlapping of actin and myosin II filaments
generates the force which divides the cytoplasm into 2
which GTPase controls the assembly of the contractile ring
RhoA - small GTPase of the Ras superfamily
