Biol 445 final material Flashcards
MDM2
and E3 ubiquitinase that destroys p53
p53: tumor suppressor or oncogene?
tumor suppressor
E2F’s effect on cyclin E
produces more of it
Cyclin E
hyperphosphorylates Rb later (CDK2)
Cyclin D
hypophosphorylates Rb early on (CDK 4/6)
Hyper-phosphorylated Rb
is free from E2F
recruits histone acetylase
Un/Hypo-phosphorylated Rb
stays bound to E2F
recruits histone deacetylaces
Rb regulates
progression through G1
biological role of abl
phosphorylates focal adhesion proteins and regulators of the actin cytoskeleton
responds to DNA damage
homologous abl
arg
abl structure is similar to?
src
Oncogenic abl mutation (in what domain?)
Myristate; carboxy terminus
Allows for “off” formation
bcr/abl fusion protein effects
increased proliferation/differentiation
increased stem cell turnover
decreased apoptosis
creates cytoskeletal/adhesion effects
Philadelphia chromosome
t9;22 causes CML and present in some adult ALLs
fuses bcr and abl genes
TCF4
turns Wnt pathway off
used by Clevers to find genes turned on by Wnt are in crypts
and genes turned off by Wnt are in villi
TCF
together with armadillo activates Wnt-responsive genes
armadillo
normally is phosphorylated by Fz
without phosphorylation, moves to nucleus and binds to TCF
wingless (wnt)
induces segmentation
places of expression take on anterior fate
binds Fz
p95 is also known as
beta-catenin; hedgehog
FAP genetic cause
APC gene
apoptosome
activates caspases
apaf bound to cytochrome-c:
assembles apoptosome
cytochrome-c
binds to apaf
bcl-2 causes:
cytochrome-c to leave mitochondria membrane
opens pores in mitochondrial membrane
bcl-2 equivalent to
ced-9
ced-3
results in apoptosis
ced-4
activates ced-3
ced-9
inhibits ced-4
p21 function
Forms inhibitory complex between CDK2 and cyclin E
Results in G1 arrest
Cell cycle arrest target of p53
p21
p53 effect on Bcl-2
Inhibition
ARF
Binds and sequesters MDM2
E2F
Hyperproliferative stress response
Active when the cell cycle is active
Activates ARF
Chk2, Chk1
Phosphorylate both MDM2 and p53
Prevent p53 degradation
Rad9
Activates Chk1
ATR
Genotoxic stress response
Activates in response to replication errors and single stranded DNA breaks
Phosphorylates Rad9
ATM
Genotoxic stress response
Activates in response to double stranded, major breaks
Activates Chk2