Nuc envelope:cell cycle homeostasis Flashcards
(25 cards)
euchromatin
light, indicates cell is transcriptionall active if in high amounts
heterochromatin
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
nucleolus
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
nuclear pores
actually filled with proteins, gated entry allows for transport in and out of the nucleus.
requires importins/exportins and a nuclear localization signal (NLS)
nuclear lamina
matrix of scaffolding proteins and lamins; important for regulation of replication, transcription and DNA repair
lamins ABC
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
laminopathies
rare genetic disorders that result from mutated lamins A/C. Cause cardiomyopathy, progeria, congenital muscular dystrophy
envelopathy
emery-dreifuss (EDMD) muscular dystrophy due to mutated Emerin. = skeletal myopathy, weakness, death
what phosphorylation events happens in mitosis?
- histone 1 is phosphorylated = chromatin condenses
2. lamins are phosphorylated = nuclear envelope breaks down
CDKs
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
MPF
M-CDK (mitotic promoting cdk pathway)
uses CDK1/cyclinB
inhibied by p21 which inhibits CDK1
Rb
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
loss of Rb
tumor develops in retinal cells of the eye, causes blindness
CDK4/6 inhibitors
used as cancer treatments because they prevent activation of Rb proliferation pathway
p53
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).
growth arrest/cytostatic cell response
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
how are cyclins degraded?
ubiquitin degradation in proteasome
intrinsic apoptosis pathway
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.
executor caspases
activate endonucleases, cleave lamins, cleave DNA repair enzymes
= apoptosis response!
BH3 family
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.
Bcl2
protein that inhibits apoptosis and promotes survival by binding Bax
extrinsic apoptosis
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.
phosphatidyl-serine (PS)
“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
annexin V
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.
