Chapter 19: Apoptosis Flashcards
how many cell types do humans have?
200
metamorphic tissues such as…must be eliminated
- tails
- gills
- digit webbing
in the nervous system _____ of early neurons are eliminated
50%
the neurons that are selected for survival are the ones that make the
proper connections with target cells
in adult tissues apoptosis is responsible for what in tissues that are undergoing cell turnover
- balancing cell proliferation
- maintaining constant cell #s
what provides a defense mechanism by which damaged/ dangerous cells can be eliminated?
apoptosis
damaged/dangerous cells are those that
- have DNA damage
- are infected by a virus
what are the steps in apoptosis?
- DNA fragmentation/chromatin condensation
- nucleus fragmentation
- cell fragmentation - membrane blebbing
- apoptotic bodies
cell fragments and apoptotic bodies are recognized and phagocytosed by
macrophages & phagocytic cells
how does apoptosis protect the surrounding cells?
by keeping all cellular material within a membrane
how do phagocytic cells recognize apoptotic bodies and cell fragments?
they recognize phosphatidylserines
what are the 3 gene products that play a key role in regulating and executing apoptosis?
- ced3
- ced4
- ced9
ced3 is a prototype of a family of mammalian proteases known as
caspases
ceds have ___________ residues in their active site and cleave after _____________ residues.
- cysteine
- aspartic acid
what are the common targets of ced3
- inhibitors of nuclear DNase
- lamins
- cytoskeleton
the mammalian homolog to ced4 is
apaf-1
ced4 binds to
caspases to promote their activation
the mammalian homolog of ced9 is
Bcl-2
members of the Bcl-2 family are both
pro-apoptotic and anti-apoptotic
IAPs are
inhibitors of apoptosis proteins
what directly inhibits caspases?
IAPs
what are the 5 targets of caspases?
- ICAD
- nuclear lamins
- cytoskeleton proteins
- golgi matrix proteins
- scramblase (PS to cell surface)
what is known as the key activator caspase?
caspase 9
caspase 9 is activated as it complexes w/
Apaf-1 & cytochrome C
caspase 9 cleaves and activates effector caspases such as
caspase 3
what are known as the central regulators of apoptosis?
Bcl-2 family
Bcl-2 is homologous to
Ced-9
Bcl-2 inhibits
apoptosis
the discovery of this regulatory of apoptosis focused on the importance of cell survival in cancer..what is it?
Bcl-2
what are the 3 functional groups of Bcl-2?
- antiapoptotic
- proapoptotic effector
- proapoptotic BH3-only
what are the 2 domains of the antiapoptotic functional group of Bcl-2?
Bcl-2
Bcl-XL
what are the 2 domains of the proapoptotic effector functional group of Bcl-2?
Bax
Bak
what are the 5 domains of the proapoptotic BH3-only function group of Bcl-2?
Bid
Bad
Noxa
Puma
Bim
under normal cell conditions BH3-only is
inactive
under normal conditions antiapoptotic protein remains
bound to proapoptotic protein
in apoptotic cells BH3-only interacts w/
antiapoptotic protein activating proapoptotic protein
what are the 3 initial signals of the intrinsic apoptotic pathway?
- Lack of GFs
- disease/infection
- cell/DNA damage
in mammalian cells death signals induce apoptosis through damage to the
mitochondria
what complex releases cytochrome C?
Bak & Bax
the Bak & Bax complex is found on the
OM of the MTCH
the release of cytochrome C from the MTCH leads to formation of the
apoptosome
where is cytochrome C normally sequestered?
in the inner membrane space of the MTCH
what components of the apoptosome are cytosolic?
apaf-1 & caspase-9
the formation of the apoptosome activates caspase-9 which activates…
caspase-3
what are the steps in DNA damage-induced apoptosis?
- DNA damage activates ATM & Chk2 kinases
- p53 is phosphorylated
- p53 activation leads to transcription of BH3-only proteins
- cell death
what is the initial signal of the extrinsic apoptotic pathway?
TNF & other cell death receptors
what are the steps in the extrinsic apoptotic pathway?
- TNF binds to receptor
- Caspase-8 is activated
- effector caspases are activated
- cleaves Bid
- mobilizes Bax and Bak
- intrinsic pathway follows
what is an example of non-apoptotic cell death?
autophagy
autophagy is a mechanism for the gradual turnover of
cell components in normal cells
in the state of starvation the degradation of components provides
energy & recycles materials
autophagy does not require caspases but rather the
accumulation of lysosomes
what is known as programmed cell death in response to infection or DNA damage?
necroptosis
TNF signaling leads to cell death by activating
RIPK3
RIPK3 phosphorylates
MLKL
MLKL complexes disrupt the
plasma membrane causing cell death
GFs that signal cell survival bind to
receptor protein-tyrosine kinases
activation of P13K leads to formation of
PIP3
