Cell cycle ( the cell cycle control system) Flashcards
operates like a timer that triggers the events of the cell cycle in a set sequence
cell-cycle control system
delay progression to M phase
malfunction
provide time for the machinery to be repaired and also prevent the disaster that
might result if the cycle progressed prematurely to the next stage
delay progression to M
based on a connected series of biochemical switches
cell-cycle control system
Where is cell-cycle control system based on?
connected series of biochemical switches
Each of connected series of biochemical switches possesses many important features that increase the?
accuracy and reliability of cell-cycle progression
the switches are in a irreversible fashion
binary (on/off)
irreversible fashion of switches would clearly be disastrous if?
if events like chromosome condensation or nuclear-envelope breakdown were only partially initiated or started but not completed.
the cell-cycle control system is remarkably _____ and _____ because backup
mechanisms allow the system to operate effectively under a variety of conditions
robust and reliable
remarkably robust and reliable, partly because of backup mechanisms
cell-cycle control system
highly adaptable and can be modified to suit specific cell types or to respond to
specific intracellular or extracellular signals.
cell-cycle control system
three major regulatory transitions
- Start (restriction point) in late G1
- G2/M transition
- metaphase-to-anaphase
cell commits to cell-cycle entry and
chromosome duplication
Start (restriction point) in late G1
Where do cell commits in Start (restriction point) in late G1
cell-cycle entry and chromosome duplication
Control system triggers the early mitotic events that lead to chromosome alignment on the mitotic spindle in metaphase
G2/M transition
control system stimulates sister-chromatid separation leading to the completion of mitosis and cytokinesis
metaphase-to-anaphase transition
G2/M transition triggers the early mitotic
events that lead to?
chromosome alignment on the mitotic spindle in metaphase
metaphase-to-anaphase stimulates
sister-chromatid separation, leading to
completion of mitosis and cytokinesis
What does the control system do if extracellular conditions are not appropriate for cell proliferation?
blocks progression through each of these
transitions if it detects problems inside or
outside the cell
Central components of the cell-cycle control system are members of a family of
protein kinases known as?
cyclin-dependent kinases (Cdks)
The activities of cyclin-dependent kinases (Cdks) ____ and ___as the cell progresses through the cycle
rise and fall
The rise and fall activities of Cdks lead to what
cyclical changes in the phosphorylation of intracellular proteins that initiate or regulate the major events of the cell cycle
Cdks are controlled by?
cyclins
four classes of cyclins
- G1/S-cyclins
- S-cyclins
- M-cyclins
- G1-cyclins
activate Cdks in late G1
G1/S-cyclin
what does G1/S-cyclin activaye
Cdks in late G1
bind Cdks soon after progression through Start and help stimulate chromosome duplication
S-cyclins
S-cyclins bind Cdks soon after progression
through?
Start
activate Cdks that stimulate entry to mitosis at the G2/M transition
M-cyclins
M-cyclins activate Cdks that stimulate
entry to?
mitosis at the G2/M transition
govern the activities of the G1/S-cyclins
G1-cyclins
single Cdk protein binds all classes of cyclins
In yeast cells
In yeast cells, a ___ Cdk protein binds all classes of ___
single
cyclins
Have four Cdks
vertebrate cells
How many Cdks interact with G1-cyclins in vertebrate cells?
Two
Out of 4 Cdks in vertebrate cells, only 2 interacts with?
G1-cyclins
How many Cdks interact with G1/S- and S-cyclins in vertebrate cells?
1
Out of 4 Cdks in vertebrate cells, only 1 interacts with?
- G1/S- and S-cyclins
- S- and M-cyclins
How many Cdks interact with S- and M-cyclins
in vertebrate cells?
1
4 different cyclin–Cdk complexes
- G1-Cdk
- G1/S-Cdk
- S-Cdk, and
- M-Cdk
How do different cyclin–Cdk complexes trigger different cell-cycle events?
Cyclin protein does not simply
activate its Cdk partner but also directs it to specific target proteins. As a result,
each cyclin–Cdk complex phosphorylates a different set of substrate proteins.
phosphorylates a different set of substrate proteins
cyclin–Cdk complex
in the absence of _____, active site in the Cdk protein is partly obscured by a protein loop
Cyclin
in the absence of cyclin, the active site in the ____protein is partly obscured by a _____ ____
Cdk
protein loop
causes the loop to move away from the active site, resulting in partial activation of the Cdk enzyme
Cyclin binding
Cyclin binding causes the ___ to move away from the ____ ___, resulting in partial activation of the ___enzyme
loop
active site
Cdk enzyme
occurs when a separate kinase, the Cdk-activating kinase (CAK), phosphorylates an amino acid near the entrance of the Cdk active
site.
full activation of the cyclin–Cdk
Full activation of the cyclin–Cdk complex then occurs when ?
Cdk-activating kinase (CAK) phosphorylates an amino acid near the entrance of the Cdk active
site
inhibits the activity of a cyclin–Cdk complex
Phosphorylation at a pair of amino acids in the roof of the kinase active site
Phosphorylation of active site by ____ inhibits Cdk activity
Wee1
_______ of active site by Wee1 inhibits Cdk activity
Phosphorylation
dephosphorylation of these sites by _____ increases Cdk activity
Cdc25 phosphatase
_____ of these sites by Cdc25 phosphatase
increases Cdk activity
dephosphorylation
Binding of ___ ____ ____ inactivates cyclin–Cdk complexes.
Cdk inhibitor proteins (CKIs)
Binding of Cdk inhibitor proteins (CKIs) inactivates?
cyclin–Cdk complexes
progression through the metaphase- to-anaphase transition is triggered by ____ ____, leading to the final stages of cell division
protein destruction
a member of the ubiquitin ligase
family of enzymes
anaphase-promoting complex or cyclosome
(APC/C)
used in numerous cell processes to stimulate the proteolytic destruction of specific regulatory proteins
anaphase-promoting complex, or cyclosome (APC/C)
APC/C are used in numerous cell processes
to stimulate the ______ ____of specific regulatory proteins. They _________ specific target proteins, resulting in their destruction in ______.
proteolytic destruction
polyubiquitylate
proteasomes
The APC/C catalyzes the ubiquitylation and destruction two major types
of proteins :
securin
S- and M-cyclins
protects the protein linkages that hold
sister-chromatid pairs together in early mitosis
securin
What does securin protect?
protein linkages that hold
sister-chromatid pairs together
destruction of securin
destroyed at metaphase
destruction inactivates most Cdks in the cell
S- and M-cyclins
many proteins phosphorylated by Cdks from S phase to early mitosis are ______
dephosphorylated
- ubiquitin ligase
- ubiquitylate CKI
proteins in late G1 - destruction of G1/Scyclins in early S phase
SCF
SCF is also responsible for the destruction
of?
G1/S-cyclins in early S phase
changes in its association
with an activating subunit—either Cdc20 in mid-mitosis or Cdh1 from late mitosis through early G1.
APC/C activity
APC/C activity
changes during the cell cycle, primarily as a result of changes in its association
with an activating subunit—either?
Cdc20 in mid-mitosis or Cdh1 from late mitosis through early G1
- depends on substrate-binding subunits called F-box proteins.
- constant during the cell
cycle
SCF activity
SCF activity depends on substrate-binding subunits called?
F-box proteins
cell-cycle depends exclusively on
post-transcriptional mechanisms that involve the regulation of Cdks and ubiquitin ligases and their target proteins
in early animal embryos
in early animal embryos cell-cycle control depends exclusively on?
post-transcriptional mechanisms
In the more complex cell cycles of most cell types, ______ ____provides an important additional level of regulation
transcriptional control
