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Molecular Cell Biology: Bcl2 Family and Apoptosis

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30 Questions

What is the role of p53 protein in the intrinsic apoptosis pathway?

To stop the cell cycle and induce repair enzymes in response to lesser DNA damage

What happens to antiapoptotic Bcl2 family members in apoptotic cells?

They bind to newly synthesized/activated proapoptotic BH3-only family members

Which type of cell death is characterized by a regulated process where the cell kills itself for the good of the organism or other cells?

Apoptosis

What is the term for the shrinkage of the nucleus, followed by chromatin condensation, in apoptotic cells?

Karyopyknosis

What is the result of proapoptotic multidomain family members binding to each other?

Formation of pores in the outer mitochondrial membrane

What is the function of p53 protein in response to larger DNA damage?

To induce apoptosis

Which protein family plays a crucial role in regulating the intrinsic apoptosis pathway?

Bcl-2 family proteins

What is the role of BH3-only Bcl2 family members?

To induce apoptosis

What is the term for the fragmentation of the nucleus in apoptotic cells?

Karyorrhexis

What is the function of p53 protein in response to lesser DNA damage?

To stop the cell cycle and induce repair enzymes

Which of the following is NOT a characteristic of apoptosis?

Inflammation

What is the term for the pathway of apoptosis that is initiated by extracellular signals, such as the binding of Fas ligand to Fas receptor?

Extrinsic pathway

What is the role of antiapoptotic Bcl2 family members in healthy cells?

To inhibit proapoptotic multidomain family members

What is the role of P53 protein in apoptosis?

To induce apoptosis

What happens to p53 protein in healthy cells?

It is broken down by the ubiquitin-proteasome system

What is the role of death ligands in the extrinsic apoptosis pathway?

To bind to their receptors

Which of the following is a function of autophagy?

Waste management

What is the term for the internucleosomal DNA cleavage that occurs in apoptotic cells?

Internucleosomal DNA cleavage

What is the result of p53 protein activation in response to DNA damage?

Induction of proapoptotic multidomain family members

Which of the following is a characteristic of necrosis?

Cell swelling

Which of the following Bcl2 family members contain only the BH3 domain?

Bad

What is the name of the complex formed by cytochrom C, Apaf1, and procaspase 9?

Apoptosome

Which of the following caspases is an initiator caspase?

Caspase 9

What is the role of p53 in the intrinsic pathway of apoptosis?

Induction of BH3-only Bcl2 family members

What is the result of the release of cytochrom C from the mitochondrial outer membrane?

Formation of the apoptosome

Which of the following is a characteristic of proapoptotic Bcl2 family members?

Contain only BH3 domain

What is the name of the protein family that includes caspase 3 and caspase 9?

Cysteinyl-aspartases

Which of the following is a result of the activation of the intrinsic pathway of apoptosis?

Release of cytochrom C from the mitochondrial outer membrane

What is the role of the multidomain-proapoptotic Bcl2 family members in the intrinsic pathway of apoptosis?

Form pores in the mitochondrial outer membrane

Which of the following is NOT a characteristic of caspases?

Activated by DNA damage

Study Notes

Bcl2 Family

  • Proapoptotic family members: BH3-only proteins, synthesized or activated as a result of apoptotic stimuli, bind antiapoptotic Bcl-2 family members
  • Examples: Bad, Puma
  • Proapoptotic multidomain family members: contain BH1, BH2, BH3 domains, inactivated by antiapoptotic Bcl-2 family members, released and form pores in the outer mitochondrial membrane
  • Antiapoptotic Bcl2 family members: contain BH1, BH2, BH3, BH4 domains, always present and active, bind proapoptotic multidomain family members

Caspases

  • Important in the effector phase of apoptosis
  • Protein family: cysteinyl-aspartases, cleave after an aspartic acid residue
  • Present in healthy cells in inactive form: procaspases, activated by cleavage as a result of apoptotic signal transduction
  • Active form: cleaves target proteins, very specific cleavage, activates/inactivates them
  • Initiator caspases: cleave effector caspases, e.g. caspase 8 and caspase 9
  • Effector caspases: cleave many different target proteins, e.g. caspase 3

Intrinsic Pathway

  • Activation of p53 induces BH3-only proapoptotic Bcl2 family members
  • Released multidomain-proapoptotic family members form pores in mitochondrial outer membrane, releasing cytochrom C to cytosol
  • Cytochrom C forms a complex with Apaf1 and procaspase 9, forming an apoptosome
  • Procaspase 9 cleaves itself to active caspase 9, cleaving effector caspases

Extrinsic Pathway

  • Receptor-mediated apoptosis: death ligands bind to their receptors

Role of p53

  • Plays an important role in intrinsic pathway
  • Transcription factor, also has functions independent of transcription
  • Always synthesized, but broken down in healthy cells
  • Activated and stabilized for DNA damage
  • Function: stops cell cycle, induces repair enzymes for lesser DNA damage, induces apoptosis for larger DNA damage

Cell Death

  • Types of cell death: regulated and not regulated
  • Regulated cell death: apoptosis, autophagy, etc.
  • Apoptosis: regulated, signal transduction, ATP required, activates under physiological and pathological conditions
  • Necrosis: not regulated, pathological circumstances, damaging effect cannot be survived
  • Morphological features of apoptosis and necrosis: stimuli, appearance, involved cells, cell nucleus, DNA, cell membrane, organelles, result, inflammation, phagocytosis

Alterations of Nucleus

  • Apoptosis: karyopyknosis, karyorrhexis
  • Necrosis: karyolysis

This quiz covers the Bcl2 family, specifically the proapoptotic family members, BH3-only proteins, and their role in apoptosis. It also explores how they bind to antiapoptotic Bcl-2 family members.

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