Lecture 5 - Exam Flashcards

1
Q

What is apoptosis?

A

Programmed cell death that is genetically encoded and tightly regulated, occurs at predictable places at predictable times

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2
Q

What is the term for uncontrolled cell death and why does it occur?

A

Necrosis - occurs in response to physical injury with rapid loss of PM integrity

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3
Q

What are some functions of apoptosis?

A

Normal development, eliminate used immune or damaged cells, provide tissue homeostasis between proliferation/cell death

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4
Q

What are markers of apoptosis?

A

Cell shrinkage, chromatin condensation, membrane blebbing, apoptotic body formation, DNA fragmentation, Phosphatidylserine flipping

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5
Q

What is the model organism for apoptosis?

A

C. elegans

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6
Q

What are the pro-survival proteins?

A

Bcl-2, Bcl-xL, Bcl-w, Mcl-1, A1 - have 4 BH domains

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7
Q

What are the pro-apoptoic proteins?

A

Bax, Bak, Bok - have 3 BH domains

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8
Q

What are the pro-survival and pro-apoptotic regulators?

A

Bim, Puma, Noxa, Bik, Bmf, Bad, Bid, Hrk - only have Bh-3 domain - fall under pro-apoptotic category

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9
Q

What family do pro-survival and pro-apoptotic proteins belong to?

A

Bcl-2 family

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10
Q

What is caspase 9?

A

The initiator of the intrinsic pathway - contains CARD - caspase recruitment domain

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11
Q

What is caspases 8,10?

A

The initiators of the extrinsic pathways - contain DED - death effector domain

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12
Q

What is caspase 3?

A

The executioner caspase

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13
Q

How is DNA fragmentation carried out?

A

Caspase 3/7 (executioner) activate removal of inhibitory unit on DFF (DNA fragmentation factor) 45/ICAD heterodimer to activate the DNAs - DFF40/CAD (caspase activate DNAse) that cuts linker DNA

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14
Q

What is the intrinsic pathway of apoptosis?

A

BH3 becomes activated by stress –> directly activates BAX/BAK –> BAX/BAK causes pores to open in mitochondrial outer membrane –> cytochrome c released and SMAC/DIABO (IAP binding proteins)–> binds with APAF1 –> activates procaspase 9 binds apoptosome –> cleaves caspase 3/7 –> leads to apoptosis

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15
Q

What does pro-caspase 9 activation require?

A

Apaf-1, cytochrome c, dATP

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16
Q

What are IAPs and what do they do? How are they regulated?

A

XIAP, cIAP, NAIP, ML-IAP - prevent cell death by binding and inhibiting caspases - negatively regulated by IAP binding proteins SMAC/DIABLO

17
Q

What are Smac (diablo)? What is analogous in drosophila?

A

Mitochondrial proteins that bind to IAPs to promote caspase activity and cell death - Smac interacts with XIAP and DIablo with cIAP - analogous in drosophila are hid/grim/repear

18
Q

How is the extrinsic pathway triggered? And what is it regulated by?

A

Triggered by death inducing cytokines like FasL/TNFalpha - where ligand binds receptor to signal to FADD (Fas-associated death domain) that contains DED to signal to procaspase 8 –> caspase 8 –> other caspases or BID –> death - regulated by FLIP

19
Q

What is DISC?

A

Death inducing signaling complex in extrinsic pathway - made up of FADD signaling to procaspase 8 and caspase 8

20
Q

What are the cancer therapeutics used to target the apoptotic pathway?

A

BH3 mimetics to inhibit Bcl2 and Bcl-x binding to free up pro-apoptotic proteins
Smac mimetics to bind and inhibit IAPs

21
Q

What does p53 have to do with apoptosis?

A

When cell senses damage mdm2 (the inhibitor) release from p53 which decides to activate repair or apoptosis of the cell

22
Q

What do CDKs do?

A

Bind different cyclins to promote cell cycle transitions

23
Q

What are cyclins degraded by?

A

SCF and APC/C

24
Q

What are the G1 CDK/cyclins?

A

CDK4/6 and cyclin D

25
Q

What are the G1/S CDK/cyclins?

A

CDK2 and cyclin E and A

26
Q

What are the mitotic CDK/cyclins?

A

CDK1 and cyclin A and B

27
Q

What is a stage in G1 in which cells become irreversibly committed to the cell cycle?

28
Q

What is the roll of CDKs in G1?

A

G1 CDKs activate E2F which is held inactive by Rb until it is released by phosphorylation - E2F then activates genes involved in DNA synthesis and stimulates transcription of genes for other cyclins

29
Q

What inhibits S phase CDKs?

A

Sic - until it is phosphorylated and dissociates and degraded by proteasomes allowing DNA replication to continue

30
Q

What inhibits Mitotic CDKs? And what activates them?

A

Wee - inhibitor must become inactivated and Cdc25 must become activate in a feedback loop

31
Q

What else inhibits S phase CDKs?

A

p27 - prevents premature activation of S phase CDKs - also is phosphorylated for degradation allowing for cyclin activation

32
Q

How do S phase CDKs trigger DNA replication?

A

Recruit MCM helicase activators to origins

33
Q

What do mitotic CDKs do in the cell cycle?

A

Promote nuclear membrane breakdown by phosphorylation of lamins and nucleoporins - promote spindle formation (centrosome disjunction) - trigger condensin complex to condense chromosomes