Nuc envelope:cell cycle homeostasis

Question 1

euchromatin

Answer 1

light, indicates cell is transcriptionall active if in high amounts

Question 2

heterochromatin

Answer 2

dark, normally just in the nucleolus, but if a cell is transcriptionally inactive (like a lymphocyte that has not started making antibodies) it can take up most of the nucleus

Question 3

nucleolus

Answer 3

synthesizes rRNA and subunits, has core of 5 acrocentric chromosomes (13,14,15,21,22) which all have rRNA genes aligned in the center for easy access

Question 4

nuclear pores

Answer 4

actually filled with proteins, gated entry allows for transport in and out of the nucleus.

requires importins/exportins and a nuclear localization signal (NLS)

Question 5

nuclear lamina

Answer 5

matrix of scaffolding proteins and lamins; important for regulation of replication, transcription and DNA repair

Question 6

lamins ABC

Answer 6

intermediate filaments, strong due to dimerization; have P sites where they can be phosphorylated for change in structure and thus regulation of replication/repair/transcription

Question 7

laminopathies

Answer 7

rare genetic disorders that result from mutated lamins A/C. Cause cardiomyopathy, progeria, congenital muscular dystrophy

Question 8

envelopathy

Answer 8

emery-dreifuss (EDMD) muscular dystrophy due to mutated Emerin. = skeletal myopathy, weakness, death

Question 9

what phosphorylation events happens in mitosis?

Answer 9

1. histone 1 is phosphorylated = chromatin condenses

2. lamins are phosphorylated = nuclear envelope breaks down

Question 10

CDKs

Answer 10

Regulate the cell cycle = cyclin dependent kinases, active only when their cyclin is bound, can be regulated by phosphorylation as well

can be blocked by CKIs which bind CDK or CDK-cyclin complex

Question 11

MPF

Answer 11

M-CDK (mitotic promoting cdk pathway)
uses CDK1/cyclinB

inhibied by p21 which inhibits CDK1

Question 12

Rb

Answer 12

Rb protein regulates G1-S restriction point; Pathway: growth factor > Ras pathway > CDK4/6-cyclin D complex active, phosphorylates Rb > Rb inactive, dissociates from EF2 transcription factors and turns on transcription for S phase genes = proliferation

Question 13

loss of Rb

Answer 13

tumor develops in retinal cells of the eye, causes blindness

Question 14

CDK4/6 inhibitors

Answer 14

used as cancer treatments because they prevent activation of Rb proliferation pathway

Question 15

p53

Answer 15

regulates G1-S restriction point, blocks synthesis phase if DNA is damage.
Can cause growth arrest via activating transcription of CKI p21, or apoptosis through intrinsic pathway (Bax).

Question 16

growth arrest/cytostatic cell response

Answer 16

p53 phosphorylated and active, binds regulatory region of p21 inducing transcription of p21. p21 is a CKI for CDK that normally activates G1/S checkpoint. = growth arrest

p53-P > binds p21 gene promoter > p21 inhibits CDK2 which keeps it from activating Rb pathway which turns on S phase transcription

Question 17

how are cyclins degraded?

Answer 17

ubiquitin degradation in proteasome

Question 18

intrinsic apoptosis pathway

Answer 18

initiated by p53 if DNA damage is too much to repair. (p53 activates Bax)

p53 phosphorylated, active, activates transcription of Bax (Bcl2/BH3 family) which causes mitochondria to release cytochrome C into cytoplasm. Cyt C activates caspase 9 (initiator caspase) which cleaves/activates caspases 3,6,7 (executor caspases) to cause apoptosis.

Question 19

executor caspases

Answer 19

activate endonucleases, cleave lamins, cleave DNA repair enzymes

= apoptosis response!

Question 20

BH3 family

Answer 20

including Bax (pro-apoptosis), Bcl2 (anti-apoptosis, binds Bax to inhibit) and tBID (pro-apoptosis through phagocytic pathway).

Family of proteins which all contain a BH3 region that allows them to bind to each other.

Question 21

Bcl2

Answer 21

protein that inhibits apoptosis and promotes survival by binding Bax

Question 22

extrinsic apoptosis

Answer 22

ligand binds DISC (death inducing signal complex) which activates it and causes it to trimerize. DISC activates executor caspase 8/10 which activates tBID. tBID acts like Bax, causes pores in mitochondrial membrane and release of Cyt C. Cyt C activates downstream caspases including 3,6,7 = apoptosis.

Question 23

phosphatidyl-serine (PS)

Answer 23

“eat me” signal for phagocytosis, normally found on inner leaflet of cell membrane, so if found on outer leaflet it indicates cell damage

Can be detected by annexin V

Question 24

annexin V

Answer 24

calcium dependent phospholipid binding protein with high affinity for PS. Can be used in assay by fluorescently tagging annexin and allowing it to bind PS to see if cell is apoptotic.

Question 25

MDR

Answer 25

multi drug resistance results from over-expression of Bcl2 which blocks Bax and causes resistance to apoptosis