26 – Cell Cycle II Flashcards
2 main things in mitosis
1 segregate your chromosomes perfectly
how to cells get rid of protein
Proteins degraded by proteasome after poly-ubiquitination
Cyclin must be poly-ubiquitinated as well
Degradation after poly-ubiquitination
o Unfolding
o Cleavage in central cavity
o Discharge of peptides
Recycled for protein synthesis
M-phase Cyclins poly-ubiquitinated by
Anaphase-Promoting-Complex
-APC/C = cyclosome
Different binding partner = different target
APC gets it target-specificity and activation from
its binding partners which activate it and target it to specific proteins.
Different binding partner = different target
how does APC work?
APC attach ubiquitin chains to cyclins to feed them into proteasome.
APC is a ….
ubiquitin ligase: a protein that attaches ubiquitin chains or ligates them onto polypeptides.
Cells hold back the Metaphase-Anaphase transition by
inhibiting APC partners
Anaphase MUST… to progress to anaphase
wait until all chromosomes are bi-oriented
How to know a chromosome is bi-oriented?
It could be force-based
When kinetochore feel pulled on both site to two opposite directions
Cohesins
physically tie tgt sister chromatids
when the metaphase to anaphase transition occurs….
Cohesin, ring shaped structure around chromosomes, is going to be physically cleaved.
WAITING = prevent…
preventing proteolysis of cohesion molecules
Separase
cut Cohesin to let go of sister chromatids
as cells wait for their chromosomes to align, they need to make sure that this ring stays intact.
separase is Kept in check (inhibited) by
Securin = block active site of separase
cells are ready to progress into anaphas
- APC in conjugation with Cdc20 will Poly ubiquitinate securin
-securin is ubiquitinated by Cdc20-APC - release separase & will separate the the cohesin molecules
- sister chromatids will come apart.
Cdc20 inhibited by
by binding to Mad 2
Mad 2
prevent Cdc20 inhibiting APC
polyubiquitinating Securin—releasing Separase
Mad2 in open conformation
Can’t inhibit Cdc20
Mad2 in closed conformation
Inhibits Cdc20
Prevent triggering anaphase transition
schematic of how Unaligned chromosomes catalyze conversion of Mad2
- open Mad2 bind to Mad1 & convert it into the closed state.
- closed Mad2 will be released back into the cytoplasm & bind to inhibit CDC 20
- closed Mad2 - Cdc20 complex= can interact with more open Mad2 in solution
-bind to an open Mad2 to produce another closed Mad2, which will then go on to inhibit more CDC 20. - every single unaligned chromosome is not only generating its own closed Mad2 (its own inhibitor)
-also the closed Mad2 is auto catalyzing the creation of more and more closed Mad2
Unaligned/unattached (not yet bi-oriented) chromosomes catalyze
conversion of Mad2
Mad1 bind to unattached chromosome
-Act as template & catalyst for creation of closed Mad2
Mad2 in closed conformation can interact with Mad2 in open conformation
Makes more Mad2 that inhibit Cdc20 = megaphone for last unaligned chromosomes to shut cell cycle down
reason that each chromosome is doing this massive amplification of the CDC 20 signal
because that 1 chromosome that’s stuck behind while all of the rest of them have aligned has to be able to scream at the top of its lungs:
Wait for me!!!!
a megaphone that allows that last one unattached chromosome to shut the entire cell cycle down all by itself.
if one chromosome was insufficient to shut the whole thing down
you’d have chromosome segregation errors all the time, and it would be a disaster for the development of multicellular organisms.
