Week 9

Question 1

How was Bcl-2 discovered?

Answer 1

BCL2 was originally identified in Croce’s lab in 1984 as the target within the breakpoint region of the t(14;18) translocation carried by patients with the follicular variant of B-cell lymphoma, from which it takes its name

Question 2

What does Bcl-2 do?

Answer 2

A protein that helps control whether a cell lives or dies by blocking a type of cell death called apoptosis

Question 3

What are some members of the Bcl-2 family of proteins?

Answer 3

• Bcl-2 associated X protein
• Bcl-xL
• Bcl-2 homologous antagonist
• Bcl-2 associated death promoter
• Bcl2l2
• BECN1
• Voltage dependent anion channel

Question 4

What are the guardians?

Answer 4

The anti-apoptotic
family members of Bcl-2

Question 5

What are the effectors?

Answer 5

The pro-apoptotic family
members of Bcl-2

Question 6

What are the locations of BAK and BAX?

Answer 6

Bax primarily localizes to the cytoplasm in healthy cells while Bak is mainly located at the MOM

Question 7

What are the initiators?

Answer 7

The pro-apoptotic family members of Bcl-2

Question 8

What can trigger the activation of apoptosis?

Answer 8

Either intrinsic cues or activation of the relevant pathways by external ligands

Question 9

What do BAX and Bak bind to?

Answer 9

Bax and Bak can be activated by direct binding of certain BH3-only proteins

Question 10

What are BAX and BAK known as?

Answer 10

The gateway to apoptosis because of their requisite roles as effectors of mitochondrial outer membrane permeabilization (MOMP), a major step during mitochondria-dependent apoptosis

Question 11

What is the relationship between the Bcl2 family and cancer?

Answer 11

Overexpression of antiapoptotic BCL2 family proteins is observed in many cancers, and can result from chromosomal translocations, gene amplification, increased gene transcription, and/or altered posttranslational processing

Question 12

What are BHS-mimetic drugs developed to do?

Answer 12

Directly activate the apoptosis machinery in malignant cells

Question 13

What is ABT-737?

Answer 13

A small molecule drug that inhibits Bcl-2 and Bcl-xL, two members of the Bcl-2 family of evolutionarily-conserved proteins that share Bcl-2 Homology domains

Question 14

What is Navitoclax?

Answer 14

An experimental orally active anti-cancer drug, which is a Bcl-2 inhibitor similar in action to obatoclax

Question 15

What are the common side effects of Navitoclax?

Answer 15

• a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness.
• diarrhoea or constipation.
• feeling or being sick.
• tiredness (fatigue)
• loss of appetite

Question 16

Is ABT-199 venetoclax?

Answer 16

Venetoclax (ABT-199): a Selective Inhibitor of B-Cell Lymphoma-2

Question 17

How long does it take venetoclax to work?

Answer 17

In the clinical study, the median time for patients to achieve some level of remission for either CR or CRh was 1 month (with a range of 0.6 to 14.3 months)

Question 18

What is a promising anti-tumor therapeutic?

Answer 18

BH3 mimetics targeting MCL-1

Question 19

Where does extrinsic apoptosis begin?

Answer 19

Outside a cell, when conditions in the extracellular environment determine that a cell must die

Question 20

What are death receptors?

Answer 20

Membrane-bound protein complexes that on binding their cognate ligand, activate an intracellular signaling cascade that results in apoptosis

Question 21

What is disc in apoptosis?

Answer 21

The death-inducing signaling complex (DISC), composed of Fas, FADD, and caspase-8, is an apical signaling complex that mediates receptor-induced apoptosis

Question 22

What is tBid?

Answer 22

A pro-apoptotic member of the Bcl-2 protein family

Question 23

What is the role of caspase-8 in apoptosis?

Answer 23

It is required to allow mouse embryo survival, and the survival of hematopoietic cells during their development and activation

Question 24

What treatments are typically associated with the increased markers of apoptosis?

Answer 24

In vitro and in vivo, effective treatment of cancer with radiotherapy or anticancer drugs

Question 25

Where is the apoptotic “point of no return”?

Answer 25

It’s commonly held to be the point at which the outer mitochondrial membrane is permeabilised, a process regulated by the Bcl-2 family of proteins

Question 26

What are the morphological characteristics of apoptosis?

Answer 26

Cell shrinking, chromatin condensation, nuclear fragmentation, and plasma membrane blebbing

Question 27

Can apoptosis occur without caspases?

Answer 27

Although the biochemical changes explain in part some of the morphological changes in apoptosis, it is important to note that biochemical analyses of DNA fragmentation or caspase activation should not be used to define apoptosis, as apoptosis can occur without oligonucleosomal DNA fragmentation

Question 28

What is a requirement of caspase-independent cell death linked with inflammation?

Answer 28

Mitochondrial DNA (mtDNA) activation of cGAS‐STING signalling

Question 29

What does caspase do in apoptosis?

Answer 29

Caspases, a unique family of cysteine proteases, execute programmed cell death (apoptosis)