20. Members Of The Bcl-2 Superfamily And Their Roles In Various Apoptotic Pathwasy

Question 1

Activation of procaspase 5 activates consequently which caspases?

Answer 1

Casepase 3,6,7

Question 2

Major class of intracellular regulators of the intrinsic pathway and how?

Answer 2

Bcl 2 family of protein by controlling the release of Cyt C and other intramembranous protein into the cytosol

Question 3

3 classes of Bcl-2 family

Answer 3

1. Proapoptotic multidomain Bcl-2 prot (BH3,1,2, TM domain) e.g. Bak, Bax “large pore”
2. Antiapoptotic multidomain Bcl-2 prot (BH4,3,1,2, TM domain) e.g. Bcl-2, Bcl-x, MCL-1 “cork of wine bottle” antagonizing Bak, Bax
3. Proapoptotic BH3 only Bcl-2 prot e.g. Bad, Noxa, Bid, Puma, Bim helping proapoptotic member from cytosol to Mt memb.
   * proapoptotic BH3 only Bcl-2 protein is the larges subclass of Bcl-2 family prot

Question 4

Mt pore types

Answer 4

• small micropore

- Bak, Bax embedded transmembrane domain capable of forming large pore

Question 5

Mechanism of opening the large pore of Bak, Bax

Answer 5

1. signals activate proapoptotic Bcl-2 protein
2. Proapoptotic Bcl-2 protein binds to antiapoptotic protein (Bcl-2, Bcl-X, MCL-1) to make a heterodimer which inhibits each other’s function
3. formation of large pore by Bak, Bax
4. Apoptosis

Question 6

Function of shared BH3 domain by all Bcl-2 familily

Answer 6

Mediating the direct interactions between pro-apoptotic and anti-apoptotic family member (dock of heterodimer)

Question 7

Activation of pro-apoptotic BH3 only Bcl-2 protein

Answer 7

In response to apoptotic(death) stimulus predominant to survival stimulus and cause translocation of Bax onto the Mt. membrane from cytosol (increasing chance of oligomerization of Bak,Bax)

Question 8

Special feature of Bad protein (pro-apoptotic only BH3 domain Bcl-2 prot)

Answer 8

Only inbibits Bcl-2, Bcl-X but not stimulate Bak, Bax

Question 9

Different types of signals activating proapoptotic Bcl-2 protein

Answer 9

Lack of survival signal -> Bad ; 살고자 하는 의지가 없음 나쁜거
Binding of death ligand -> tBid ; 비딩할땐 죽을 각오를 하고
p53 -> Noxa, tBid, Puma ; 53잡고 녹사가 퓨마를 비딩
ER stress -> Bim ; 얼 스트레스는 눈에서 빔을 쏘게해