Cyclins, CKIs, ATM, ATR, and Caspases Flashcards Preview

biochem final > Cyclins, CKIs, ATM, ATR, and Caspases > Flashcards

Flashcards in Cyclins, CKIs, ATM, ATR, and Caspases Deck (29)
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1
Q

The components of the G1 Cdk complex

A

Cyclin D, and Cdk4 or Cdk6

2
Q

Components of the G1/S Cdk complex

A

Cyclin E, Cdk2

3
Q

Components of S Cdk complex

A

Cyclin A, Cdk1 Cdk2

4
Q

Components of the M Cdk complex

A

Cyclin B, Cdk1

5
Q

Targets of the APC

A

Securin proteins linking sister chromatids, and the S and M Cdk complexes.

6
Q

What is the function of the ATM protein family in relation to the cell cycle

A

The “Ataxia Telangiectasia Mutated” proteins. Are safety checking proteins which scan dsDNA for strand breaks.

If these ATM proteins detect DNA damage they activate DNA repair and/or apoptotic pathways via their kinase activity.

ATM activates Chk1 and Chk2 kinases, which then activate p21 and p53 (Cdk inhibitors, CKIs)

7
Q

At what points in the cell cycle are ATM proteins important?

A

Many.

At cell cycle re-entry, ie: G1 -> S or G0 -> S

From G2 -> M

Metaphase -> Anaphase

Anaphase -> Telophase

8
Q

Effects of p53

A

p53 stimulates transcription of p21

p21 binds and inhibits G1/S Cdk complex and S-Cdk complexes.

9
Q

Are cyclins expressed highly before, during, or at the end of their corresponding cell cycle phase

A

Cyclins rise just prior to the start of their indicated phase, and remain high throughout, then must fall to allow the phase to end.

10
Q

What is needed for a cyclin dependent kinase to be fully active

A

1) binding to its target cyclin

2) activation by the Cdk-Activating Kinase. CAK.

11
Q

What is the main cyclin target of mitogens, and how do mitogens regulate the cyclin levels?

A

To increase levels of G1/S Cdk complex, cyclin E.

Mitogen signal cascades phosphorylate and inactivate the inhibitory Retinoblastoma Family proteins. (RB proteins).

RB proteins then release E2F transcription factors to which they were bound.

E2F Transcription factors can then induce the G1/S and S cyclin expression.

12
Q

What are the main gene targets induces by the G1-Cdk complexes

A

The E2F family of proteins.

E2F proteins themselves then induce other G1/S and S cyclins and other initiating factors for cell cycle entry.

13
Q

What other kinases are involved in the downstream signaling of ATM and ATR proteins?

A

The Chk1 and Chk2 protein kinases.

14
Q

Initiator caspases

A

Caspase 2, 8, 9, 10

15
Q

Executioner caspases

A

3, 6, 7

16
Q

Inflammatory caspases

A

1, 4, 5

Caspase 1 was first called ICE, Interleukin-1-converting enzyme.

17
Q

How are caspases activated?

A

By proteolytic cleavage of procaspases -> active caspases.

18
Q

Targets of the initiator caspases

A

Other procaspases, both initiators to amplify the signal and executioners

19
Q

Targets of executioner caspases

A
Among their very many targets:
Nuclear Lamins 
Nuclear inhibitors of Endonucleases
Cytoskeletal proteins
Cell-Cell adhesion proteins
20
Q

What are SMACs

A

Second Mitochondria-derived Activator of Caspases.

Mitochondrial proteins that are released to the cytosol following permeation of mitochondrial membrance by caspases.

SMACS bind and inhibit IAP proteins (Inhibitors of Apoptosis)

Part of the Intrinsic Apoptosis pathway.

21
Q

Mitochondrial factors that are released to stimulate the intrinsic pathway of apoptosis.

What protein transport them across the membrane?

A

Cytochrome c

SMACs

The MAC channel Mitochondrial Apoptosis-induced Channel,

aka

The Mitochondrial Outer Membrane Permeabilization Pore.

22
Q

Downstream target of Cytochrome c in apoptosis

A

Apaf-1 and ATP, and then procaspase 9

Cytochrome c-Apaf-1-ATP complex binds to pro-caspase 9.

This is the apoptososme.

23
Q

What comprises the apoptosome

A

Cytochrome c, Apaf-1, ATP, and procaspase 9.

24
Q

What is Apaf-1

A

Apoptotic Protease Activating Factor-1

Part of the apoptosome.

25
Q

Describe the intrinsic apoptotic pathway

A

1) Mitochondria are induced to swell and/or are porated via the MAC channel.
2) Cytochrome c and SMACs are released
3) Cyctochrome c complexes with procaspase 9 and ATP,
4) This complex binds Apaf-1 forming the apoptosome.
4) Procaspase 9 is cleaved to active caspace 9 in the apoptosome.
5) Caspase 9 activates Caspace 3 molecules (and other 9’s)
6) Caspase 3 executioner caspace initates apoptosis

26
Q

What proteins can inhibit the formation of the MAC pore

A

Bcl-2 family of anti-apoptotic proteins.

27
Q

Anti-Apoptotic proteins

A

Bcl-X Bcl-2

28
Q

Pro-apoptotic, non-caspase proteins

A

BAX, BAD, BID, BAK

promote mitochondrial permeation.

29
Q

What pathway is Apoptosis Inducing Factor part of?

A

The Caspase-Independent pathway.

It is ALSO released from the mitochondria.