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Printable Handouts
Navigable Slide Index
- Introduction
- How are CDKs involved in S/G2/M phases?
- CDK complexes trigger steps in DNA replication
- CDK complexes trigger steps in mitosis
- DNA damage checkpoint
- DNA damage shuts down the cell cycle motors
- DNA damage triggers p21 expression
- Segregation checkpoint
- CDK complexes trigger chromatic separation
- CDK complexes trigger chromatic separation: BUB
- S and M phase checkpoints
- Cell cycle and chemotherapy
- Cancer treatments act by inducing mitotic or DNA damage
- Cancer therapies: proliferating cell-centric to target-specific
- Alteration of all cell cycle players detected in cancer
- Proliferation controls: targeted therapies
- Oncogenic funnel: targeted drugs
- Cyclin D-CDK4 in cancer
- Cyclin D-CDK4 in pancreatic cancer
- CDK4/6-specific inhibitors
- Palbocicib-PALOMA 3, PFS
- Targeting only CDK4 allows resistance to develop when CDK2 is activated
- Future: combination therapies
- Thank you for listening
Topics Covered
- Proliferative and antiproliferative signals
- Oncogenic funnel
- Cyclins and CDKs
- Mitogenic signals
- Retinoblastoma protein
- Mitosis
- Cell arrest
- Chemotherapy
- Target-specific cancer therapy
- Palbocicib-PALOMA 3
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Blain, S. (2023, March 30). The mammalian cell cycle: the autonomous stage and cell cycle targets in cancer therapy [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 21, 2024, from https://doi.org/10.69645/WLVB7809.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Stacy Blain is the co-founder and an equity holder in Concarlo Therapeutics, Inc, which is developing therapies based on cell cycle regulation.
The mammalian cell cycle: the autonomous stage and cell cycle targets in cancer therapy
Published on March 30, 2023
21 min
Other Talks in the Series: The Molecular Basis of Cancer
Transcript
Please wait while the transcript is being prepared...
0:04
We talked a lot
about the role of
the CDKs in G1 phase or
the cell responsive phase,
how they interpret the
extracellular signals
and help drive the
cell into the S phase,
into the autonomous phase.
But the cyclin CDKs are also
involved in the cell
autonomous phase.
They are the hammers that
will stop the cell cycle
in response to the
DNA damage errors
or the mitotic errors.
0:29
We know that just to
review the pre-replication
complexes,
assembled in G1,
that means all the
proteins that will sit
on the origins of replication
in our DNA waiting for that
signal to start replicating.
And that signal is
really the cyclin E,
cyclin A, CDK2-dependent
signaling.
They actually will phosphorylate
members of the pre ARC complex,
allowing that
replication to begin,
elongation will
happen and then as we
get to M-phase when
we're starting to
replicate the cell to
undergo cytokinesis
that also requires CDK activity.
The CDKs are really
integral in catalyzing
the sequential
activation of all of
the steps from S-phase
through M-phase.
1:18
Here's an example of this.
You probably remember from
your earlier biology classes,
the mitosis phase,
we start from an interface
style which has disordered
DNA in the nuclear membrane
and then we have the
different phases of mitosis,
from prophase all the
way to telophase.
In prophase, the chromosomes
start getting condensed so
that they will not
get broken during
mitosis, then during metaphase,
they're going to
get separated and
lined up on the metaphase plate
so that as the cell and
telophase undergoes
that separation,
pulling the chromatids to
either side of the cell,
getting ready for
the closing off of
these two new birthing, these
two new daughter cells.
CDKs trigger all the
steps in this process.
They trigger chromosomal
condensation,
they trigger nuclear
envelope disassembly,
so that the mitotic spindle
can actually get
to the chromatids
and they trigger the assembly
of the mitotic spindle itself.
Conversely, they
also trigger all
of the steps that
finish this process,
so the chromosome
decondensation as
the chromosomes fall out
of that chromatid state,
the nuclear envelope
has to be reassembled,
and then the spindle
has to be disassembled
and cell-cycle signals
in a stepwise fashion,
catalyzing each of these steps.
Their importance is emphasized
as we move through
the cell cycle.
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