Cell Cycle: Start/Restriction Point & S Phase Flashcards
The presence of each cyclin rises and falls at distinct points of the cell cycle. True or false?
True
Which cyclin is highest during S phase?
S-cyclin (Cyclin A)
Which cyclin is highest during G1?
G1/S-cyclin (cyclin E)
Which cyclin is highest during M phase?
M-cyclin (cyclin B) and decreasing S-cyclin (cyclin A)
Which cyclin is highest during G2?
S-cyclin (cyclin A) with M-cycling (cyclin B) rising
Familiarize yourself with this figure.
There are ___ classes of cyclins, each of which binds and activates specific ______..
Four
Cyclin-dependent kinases (Cdks)
There are four classes of cyclins: ____, ______, ______, and _____.
G1
G1/S
S
M
The cyclin and cyclin-dependent kinase complex G1-CDK in yeast is composed of ___________ and _________.
Cyclin 3 (Cln3)
Cyclin-dependent kinase 1 (CDK1)
The G1-CDK complex in mammals is composed of ____________ and _______________.
Cyclin D
Cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6)
The G1/S-CDK complex for yeast is composed of ________ and/or ___________ and ____________.
Cyclin 1 and cyclin 2 (Cln1, Cln2)
CDK1
The G1/S-CDK complex in mammals is composed of ________ and _____________.
Cyclin E
CDK2
The G1-Cdk complex in vertebrates is composed of cyclin ___ and cyclin-dependent kinases ____ and ____. In yeast, this same complex is composed of cyclin (Cln) _____ and cyclin-dependent kinase _____.
Cyclin D
Cdk4 &Cdk6
Cln3
Cdk1
The G1/S-Cdk complex in verebrates is composed of cyclin ____ and cyclin-dependent kinase _____ while in yeast it is composed of cylcin (Cln) _____ and cyclin-dependent kinase ____.
Cyclin E
Cdk2
Cln1, 2
Cdk1
In yeast, G1 cyclin synthesis is stimulated by _________________ and ________________.
Nutrient accumulation and availability
Cell growth (i.e., size)
In mammalian cells, G1 cyclin synthesis is stimulated by __________, ________________, and ___________.
Nutrient accumulation and availability
Cellular growth (size)
Growth factor stimulation
The S-Cdk complex is composed of cyclin _____ and Cdk ____ and ____ in vertebrates and cyclin (Clb) ______ and Cdk1 in yeast.
Cyclin A
Cdk2 & Cdk1
Clb5, 6
Complete the table.
G1-Cdk, Cdk 4 & Cdk6
Cyclin A
Cdk1
Complete the table
G1-Cdk, Cdk4 & Cdk6
Cyclin E
Cyclin A, Cdk2 & Cdk1
M-Cdk, Cdk1
Complete the table.
G1-CDK, Cyclin D, Cdk4 & Cdk6, Cln3, Cdk1
Cyclin E, Cdk1
Cyclin A, Cdk2 & Cdk1, Cdk1
M-Cdk, Cdk1
Complete the table.
G1-Cdk, Cyclin D, Cdk4 & Cdk6, Cln3, Cdk1
G1/S-Cdk, Cyclin E, Cdk2, Cln1, 2, Cdk1
S-Cdk, Cyclin A,Cdk2 & Cdk1, Clb5, 6, Cdk1
M-Cdk, Cyclin B, Cdk1, Clb1, 2, 3, 4, Cdk1
In the M-Cdk complex, cyclin _____ and cdk _____ are present in vertebrates and cyclin ________ and cdk ____ in yeast.
Cyclin B
Cdk1
Clb 1, 2, 3, 4
Cdk1
The G1/S boundary is the “start” or _______________ point.
Restriction
What do cyclin dependent kinases do?
Regulate progression of the cell cycle at distinct stages
Cyclin-dependent kinases regulate progression at distinct stages of the _______ cycle.
Cell
Cyclin-dependent kinases can be regulated by _________ binding, ____________________, and ________________ binding.
Cyclin
Phosphorylation
CDK inhibitory proteins (CKIs)
What are three ways in which cyclin-dependent kinases (CDKs) are regulated?
(1) Binding of their respective cyclins,
(2) phosphorylation, which can activate or deactive them, and
(3) binding of CDK inhibitory proteins (CKIs)
What does CKI stand for?
Cyclin-dependent kinase (Cdk) inhibitory proteins
In yeast, G1 cyclin synthesis is stimulated by _________________ and ________________________.
Nutrient accumulation and availability
Cellular growth (increase in size)
In mammals, G1 cyclin (cyclin D) synthesis is stimulated by __________________, ____________________, and ________________.
Nutrient accumulation and availability
Cellular growth
Growth factor stimulation
What is the primary difference between yeast and mammalian cells regarding G1 cyclin synthesis?
Mammalian cells require growth factor stimulation
For all other cyclins, each active _______ initiaties a wave of ____________ activity, which produces a new _______.
Cdk
Transcriptional
Cyclin
How are cyclins degraded in the cell?
Ubiquitin-dependent proteolysis
What is required for ubiquitin-dependent proteolysis during the cell cycle?
Two E3 ubiquitin-ligases:
- SCF complex
- APC/C complex (anaphase promoting complex or cyclosome)
What does APC/C complex stand for?
Anaphase promoting complex or cyclosome
The SCF complex is active throughout the cell cycle but only recognizes _______________ targets.
Phosphorylated
What are two targets of the SCF complex?
G1 cyclins and CKIs (cyclin-dependent kinase inhibitors)
How does the SCF complex recognize its targets G1 cyclins and CKIs (cyclin-dependent kinase inhibitors)?
Phosphorylation
When is APC/C (anaphase promoting complex or cyclosome) active?
When phosphorylated by the M-cyclin/Cdk complex at the metaphase/anaphase transition
What phosphorylates APC/C (anaphase promoting complex or cyclosome)?
The M-cyclin/Cdk complex (cyclin B/Cdk1)
What does APC/C target?
Proteins that possess destruction box motifs (recognition sites for APC/C)
What proteins have destruction boxes?
S-cyclin (cyclin A), M-cyclin (cyclin B), and proteins that connect sister chromatids
What are the three targets of APC/C?
- S-cyclin (cyclin A)
- M-cyclin (cyclin B)
- Proteins that connect sister chromatids
In the absence of phosphorylation, ____________________________ (Cdks) still have activity but are much lower.
Cyclin-dependent kinases
Cyclin-dependent kinases (Cdks) are more active when ___________________.
Phosphorylated
CDKs are phosphorylated by ____________.
CDK activating kinases (CAKs)
CAKs (CDK activating kinases) are active throughout the cell cycle and _________________ the amino acid ____________ at the active site.
Phosphorylate
Threonine
Phosphorylation of the amino acid threonine by CAKs (CDK activating kinases) at the active site of CDKs increases their activity but is not the ______________ step.
Rate-limiting
What kinase phosphorylate and inhibit mitotic CDKs?
Wee1 kinases
What do Wee1 kinases phosphorylate on CDKs?
Tyrosine and threonine residues in the ATP binding site of CDK
Wee1 kinases phosphorylate a tyrosine and threonine residue in the _______________ site of CDK, which potently inhibits CDK activity.
ATP-binding site
How are phosphorylations completed by Wee1 kinases removed?
Cdc25 phosphatases
________ phosphatases dephosphorylate and therefore ___________ mitotic CDKs inhibitied by Wee1 kinase phosphorylation.
Cdc25
Activate
How many classes of CKIs are present in mammalian cells?
4
What does CKI stand for?
CDK inhibitors
What are the four classes of CKIs (CDK inhibitors) in mammalian cells?
- Wee1 kinases
- INK4 (G1 CDK inhibitors)
- p21CIP (G1/S and S CDK inhibitors)
- p27<strong>KIP1</strong> (G1/S and S CDK inhibitors)
What does INK4 stand for?
Inhibitors of kinase 4
What inhibits G1 CDKs (CDKs 4 & 6)?
INK4 (inhibitors of kinase 4)
How does INK4 (inhibitors of kinase 4) (a CKI) inhibit CDK4 and CDK6 in the G1 phase?
INK4 binds them, preventing cyclin binding
When is INK4 most likely to be expressed?
In response to excessive growth stimulation because it inhibits CDKs 4 & 6 from binding cyclin D
What does the “p” stand for in p21CIP and p27KIP1?
Protein
What are the G1/S (CDK2) and S (CDK2 & 1) CDK inhibitors (CKIs)?
p21CIP and p27KIP1
How do p21CIP and p27KIP1 act as CKIs (CDK inhibitors)?
Binding G1/S and S cyclin/CDK complexes, inhibiting CDK activity
As the activity of a particular CDK begins to increase, one of its targets is the ___________ that is trying to inhibit it.
CKI (CDK inhibitor)