Bcl-2 family

Bcl-2 family

regulators of apoptosis

regulators of apoptosis

Jakub Kubiak

Jakub Kubiak

Short history of Bcl-2

Short history of Bcl-2



Discoverd in B-cell

Discoverd in B-cell

lymphoma

lymphoma



T(14:18)

T(14:18)

translocation

translocation

BCL-2

BCL-2

gene pleaced

gene pleaced

next to the Ig heavy

next to the Ig heavy

chain locus

chain locus



Proto-oncogene

Proto-oncogene



Play a role in

Play a role in

apoptosis

apoptosis

Apoptosis – what’s that?

Apoptosis – what’s that?



From Greek – falling of

From Greek – falling of



Name suggested by prof Cormack

Name suggested by prof Cormack



First featured by Kerr, Wylie and Currie

First featured by Kerr, Wylie and Currie



Cell death progamm

Cell death progamm

Apoptosis – what does it

Apoptosis – what does it

for?

for?

Features of apoptosis

Features of apoptosis



Blebbig cell surface

Blebbig cell surface



Organelle

Organelle

compaction

compaction



Chromatin

Chromatin

condensatation

condensatation

and cleavage by

and cleavage by

endonuclease

endonuclease



Cell fragmentation

Cell fragmentation



Phagocytosis

Phagocytosis

Failure of apoptosis may

Failure of apoptosis may

lead disease

lead disease



Cancer

Cancer



Neurodegenration

Neurodegenration



Autoimmune disease

Autoimmune disease



Persistant infections

Persistant infections



Ischaemia

Ischaemia



AIDS

AIDS

Bcl-2 family

Bcl-2 family



3 main groups

3 main groups



Similar

Similar

domains: BH1,

domains: BH1,

BH2, BH3

BH2, BH3



Opposite

Opposite

activity: pro-

activity: pro-

and anti-

and anti-

apoptotic

apoptotic

Structure of Bcl-x

Structure of Bcl-x

L

L



7 alfa–helices

7 alfa–helices



3 domains BH1, BH2

3 domains BH1, BH2

and BH3

and BH3



BH1 & BH2 death

BH1 & BH2 death

receptor domain

receptor domain

(mutations in these

(mutations in these

domains abolish anti-

domains abolish anti-

apoptotic activity)

apoptotic activity)



BH3 death domain

BH3 death domain



Transmembrane

Transmembrane

domain

domain

Mechanism of regulation -

Mechanism of regulation -

simply

simply



Bcl-2 regulates

Bcl-2 regulates

activation of

activation of

caspases

caspases



Bcl-2 and BAX

Bcl-2 and BAX

dimerise and

dimerise and

loose their activity

loose their activity



Apoptosis depend

Apoptosis depend

on level of pro-

on level of pro-

and antiapoptotic

and antiapoptotic

members of Bcl-2

members of Bcl-2

family

family

Regulation – less simply

Regulation – less simply



Very

Very

complicated

complicated



Real very

Real very

coplicated

coplicated



Mechanism of

Mechanism of

regulation

regulation

unknown, only

unknown, only

hypothesis

hypothesis

Cancer caused by Bcl-2

Cancer caused by Bcl-2



Bcl-2 caused cancer by impair apoptosis

Bcl-2 caused cancer by impair apoptosis



Bcl-2 is overexpressed

Bcl-2 is overexpressed



Cancer cells don’t go under apoptosis

Cancer cells don’t go under apoptosis



Cancer cells are less vulnerable to

Cancer cells are less vulnerable to

chemotherapy and radiotherapy

chemotherapy and radiotherapy

Treatment

Treatment



Bcl-2 antisense therapy (decreas the

Bcl-2 antisense therapy (decreas the

number of Bcl-2)

number of Bcl-2)

Bcl-2 family proteins are

Bcl-2 family proteins are

intensively examined

intensively examined



Reserches on many kinds of cancer

Reserches on many kinds of cancer



Reserches on apoptosis

Reserches on apoptosis



But still many informations remain

But still many informations remain

unknown

unknown

Some interesting links about

Some interesting links about

apoptosis and Bcl-2 family

apoptosis and Bcl-2 family

http://users.rcn.com/jkimball.ma

http://users.rcn.com/jkimball.ma

.ultranet/BiologyPages/A/Apoptos

.ultranet/BiologyPages/A/Apoptos

is.html#Bcl-2

is.html#Bcl-2

http://www.portfolio.mvm.ed.ac.u

http://www.portfolio.mvm.ed.ac.u

k/studentwebs/session2/group28/b

k/studentwebs/session2/group28/b

cl2.html

cl2.html

http://www.celldeath.de/encyclo/

http://www.celldeath.de/encyclo/

aporev/aporev.htm

aporev/aporev.htm

Thank you

Thank you