Exam IV: Chapter 18

cyclin D

what is the cyclin for early G1?

cyclin E

what is the cyclin for late G1/early S phase

cyclin A

what is the cyclin for S phase?

Apaf-1

adaptor in cytosol for cytochrome C

cyclin B

what is the cyclin for mitosis?

Cdk4 and Cdk6

what is the partner for cyclin D?

Cdk2

what is the partner for cyclin E?

Cdk2

what is the partner for cyclin A?

Cdk1

what is the partner for cyclin B?

cdc6

helicase inhibitor

dna replication

regulation system for…


1. cdc6 bound to origin recognition complex
2. DNA helicase binds
3. cdc6 phosphorylated
4. cdc6 releases (loaded origin)
5. cyclin A/cdk2 phosphorylate helicase
6. helicase runs (origin fired)

cdk1

confirms that all origins were fired

origin replication complex

dogpile of proteins on origin of replication

pre-RC

ORC + dna helicase (w/o Pi)

DNA damage

regulation for …


1. nick in double strand during G1
2. ATM complex adds Pi to p53
3. p53 protein acts as transcription factor for p21 gene
4. p21 proteins made
5. p21 inhibits cyclin E/cdk2 activity by conformation change or blocking active site


1. Rb cannot be inactivated
6. no progression through S phase

ATM

searching for doble stranded breaks in DNA

BRCA1 + BRCA2 combined kinase activity

cdk

cyclically activated protein kinase

proteolysis

process of cyclin destruction via proteasome

Rb

process for regulation of …


1. mitogen binds to RTK
2. cdk6, cdk4, cdk2 activated
3. cdks add Pi to RB
4. Rb dissociates (inactivated)
5. transcription regulator (E2F) released

E2F

transcription factor for S-phase activation

DNA synthesis

regulation of …


1. mitogen binds
2. RTK activation
3. Ras pathway
4. MAP pathway


1. cyclin D production (via gene expression)
2. Myc production
5. Cdk4/6 activation
6. Rb inactivation
7. E2F release


1. cyclin E/A production

\

delayed-response

when the gene expression happens a while after the initial signaling

Myc

transcription regulator for cdk4 and cdk6

hyperphosphorylated

have a ton of Pi

i.e. inactive Rb

hypophosphorylated

has less than usual Pi

i.e. active Rb

Cdk inhibition

ways of …

* inhibitor on ATP site
* inhibitor of Cdk
* \

Rb

retinoblastoma protein (not the cancer)

p53

triggers p21 and other Bad proteins

protoncogene

normal encourager of cell proliferation

oncogene

mutated encourager of cell proliferation

WAY overactive

tumor supressor

prevents cell proliferation

cdc25

activates cdk1/cyclin B

CAK

Cdk-activating kinase

turns on M-Cdk

Wee1

Cdk-inhibitory kinase

turns off M-Cdk

M-Cdk

regulation for activating …


1. cyclin B binds to Cdk1
2. CAK puts on a Pi to activate
3. Wee1 puts on a Pi to inhibit
4. Cdc25 takes off inhibitory Pi
5. M-Cdk activates

occurring in G2

prophase

condensing into chromosomes; fragmenting nuclear envelope

prometaphase

moving sisters to the metaphase plate

phosphorylating nuclear lamins/pores

metaphase

being lined up on the metaphase plate

anaphase

pulling sisters apart

telophase

reforming the nuclear envelope

kinetochore

where sisters are bound together

cohesin

what holds the legs of sister chromatids together

condensin

what help pack single sisters in chromosomes

triggered by cyclin B + Cdk1

condensin II

helps further pack sisters in prophase

condensin I

final helper needed to pack sisters in pro metaphase

chromosome condensation

process for …


1. cohesin binds to tether sisters
2. condensin II binds
3. condensin I binds

securin

inhibitor of sesperase

seperase

proteolytic enzyme that cleaves cohesin rings

APC

ubiquinase for securin

spindle fibers

microtubules that connect to sisters to pull them

centrosome

produces microtubules

lamin

filaments that hold up the nuclear envelope

nuclear envelope

made up of lamins and nuclear pore proteins

* components are phosphorylated to destroy this

apoptosis

controlled cell death


1. commitments
2. execution
3. clearance

commitment

taking up a signal for apoptosis

execution

actively working to kill the cell

clearance

cleaning up dead cells

membrane blebbing

forming bubbles of membrane around the contents of a destroyed cell

cell lysing

cutting open a cell and allowing its contents to spill out

* leads to inflammation

caspase

cystein protease that cleave proteins leading to apoptosis

zymogen

inactive enzyme

TNF

tumor necrosis factor 

* follows the same pathway as Fas

death domain

enzymatic region that recruits procaspases

procaspase

inactive caspase

extrinsic pathway

stimulus coming from outside the cell

intrinsic pathway

stimulus being produced by the cell

caspase 8

most important caspase

initiator caspase

caspase that will turn on others

executioner caspase

caspase that actually chops proteins leading to apoptosis

caspase

ways to activate…

* forced crowding
* cleavage + rearrangment

apoptosis

process for extrinsic …


1. lymphocyte with Fas ligand arrives
2. Fas ligand binds to Fas death receptor
3. death receptor recruits FADD
4. FADD binds to caspase 8 with death effector domain
5. caspase 8 cleaved and activated
6. caspase 8 cleaves other caspases

apoptosis

process for intrinsic …


1. BAX and BAK form mitochondrial pores
2. cytochrome C leaks into the cytosol
3. adaptor activated by cytochrome C
4. multiple units form apoptosome
5. apoptosome recruits procaspase 9
6. combine and activate procaspase 9
7. activates caspase 3
8. caspase cascade

CAD

activated to fragment DNA

iCAD

inhibitor for CAD which prevents apoptosis

BAX BAK

pro-apoptotic proteins

* dimerize to make mitochondrial pores

BcLXL Bcl2

anti-apoptotic proteins

* dimerize with BAX/BAK to clog pores

p53

regulation of pro-apoptotic proteins via …


1. DNA damage
2. ATM phorphorylates p53
3. p53 serves as a transcription factor for promoters
4. pro-apoptotic proteins produced
5. anti-apoptotic proteins inhibited

mitogen

extracellular division signal that binds to surface receptor

survival factor

prevents apoptosis

ORC

origin replication complex

* dogpile of proteins that stay on origin of replication

contractile ring

divides cytoplasm by cinching in

dynamic instability

constantly adding and removing spindle fibers

* length of spindles controlled by rate of addition/subtraction

necrosis

damaged cells exploding leading to inflammation

myostatin

protein which inhibits overactive muscle cell division/growth

growth factor

leads to increased cell synthesis and prevents cell degradation