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Printable Handouts
Navigable Slide Index
- Introduction
- The cell cycle
- Crystal structure of Cdk2 bound to cyclin A
- Periodicity in cyclin expression
- Regulation of Cdks
- Focusing on Cdk2
- Cdk2
- Cdk2-/- knockout mice
- Cdk2-/- knockout mice are viable
- Atrophy in testis of Cdk2-/- mice
- Absence of oocyte development in Cdk2-/- mice
- Expression of cell cycle regulators
- Kinase activity and Cdk/cyclin complexes
- Growth defect in Cdk2-/- MEFs
- Cdk complexes and activity in MEFs
- Cdk2-/- MEF analysis after starvation
- Cdk activity in synchronized MEFs
- Delayed immortalization in Cdk2-/- MEFs
- Summary Cdk2
- Is there another gene that compensates for Cdk2?
- The Retinoblastoma (Rb) protein pathway
- Cdk2-/-Cdk4-/- double knockout mice
- Double mutants die around E15
- Heart defects in Cdk2-/-Cdk4-/- embryos
- In vivo proliferation in Cdk2-/-Cdk4-/- embryos
- Hypophosphorylated Rb
- Impaired proliferation in Cdk2-/-Cdk4-/- MEFs
- S phase entry defect in Cdk2-/-Cdk4-/- MEFs
- Rb phosphorylation in Cdk2-/-Cdk4-/- MEFs
- Rb defect in Cdk2-/-Cdk4-/- MEFs
- Senescence in Cdk2-/-Cdk4-/- MEFs
- HPV-E7
- HPV-E7 mutants
- Effect of Cdk2-/-Cdk4-/- on Cdk1 expression
- Summary Cdk2-/-Cdk4-/-
- What is going on in the S phase?
- The p27 network
- Cdk2-/-p27-/- double knockout mice
- Cdk2-/- and p27-/- mice vs. WT
- Cdk2-/-p27-/- mice
- Ovary tumors in Cdk2-/-p27-/- mice
- Pituitary tumors
- Normal levels of cell death in the thymus
- High levels of S phase and mitosis in thymus
- Cdk activity in the absence of Cdk2 and p27
- Cdk1 binds to p27 and cyclin E
- Proliferation of MEFs
- Silencing of Cdk1 in Cdk2-/- MEFs
- Summary Cdk2-/-p27-/-
- Cdk1/cyclin E complexes can drive S phase
- Cdk1 compensates for Cdk2
- Premature translocation to the nucleus of Cdk1
- DNA damage response in Cdk2-/- knockout mice
- Response to gamma-irradiation in MEFs (1)
- Response to gamma-irradiation in MEFs (2)
- Partial hepatectomy model for in vivo response
- Molecular outcome of gamma-irradiation
- Co-localization of Cdk1 and p21
- Proliferation of MEFs after irradiation
- Cdk2-/- mice are sensitive to gamma-irradiation
- DNA damage: comet assay
- DNA damage: gamma-H2AX staining
- Disturbed kinetics of DNA damage foci
- DNA damage pathway
- DNA damage in the absence of Cdk2
- Acknowledgments
Topics Covered
- Cell cycle regulation during mouse development and adulthood
- Cyclin-dependent kinases (Cdks)
- The genetic pathways for cell cycle regulation
- Cdk1, Cdk2, Cdk4, and Cdk6
- The in vivo functions of Cdk2
- Compensation between different Cdk/cyclin complexes
- Genetic interaction between Cdk2 and Cdk4
- Control of the G1/S phase transition by the Retinoblastoma protein (Rb)
- DNA damage response in the absence of Cdk2
- p27Kip1 inhibits Cdk1 in vivo
- Cdk1/cyclin E complexes promote S phase
- Cdks and tumors
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Talk Citation
Kaldis, P. (2020, May 28). Mouse models to investigate cell cycle and cancer [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/ZCMI1884.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Philipp Kaldis has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Update Available
The speaker addresses developments since the publication of the original talk. We recommend listening to the associated update as well as the lecture.
- Full lecture Duration: 61:43 min
- Update Interview Duration: 11:32 min
A selection of talks on Cancer
Transcript
Please wait while the transcript is being prepared...
0:00
This is a presentation by Philip Kaldis
from the Institute of Molecular and
Cell Biology, IMCB from Singapore.
I will tell you about our
investigations into the regulation of
the cell cycle in vivo,
using mouse model systems.
0:17
The cell cycle is divided in four
different phases 'S' phase where DNA is
replicated and the 'M' phase or
mitosis where the cells physically divide.
And in between we have the so
called gap phases G1 and G2.
These gap phases are actually very
important in preparing the events in 'S'
phase in mitosis and also to monitor
the completion of these events.
So they contain the so
called check points.
The transitions between one cell cycle
phase to the next one is promoted by
cyclin-dependent kinases and on the slide,
I've indicated some of these kinases.
0:56
Cyclin-dependent kinase belong to
a superfamily of protein kinases,
consisting of 20 members in mammals and
generally Cdks are small molecules
of about 30 to 40 KiloDalton.
They consist of a better rich N-terminus,
and a helix C-terminus and
in between, you can see the ATP
binding sites in here as well as
the so-called T-loop or
activation segment in red or in yellow.
Now, on the right side, in purple,
you see a fragment of cyclin A.
1:32
Cyclin molecules are highly unstable
proteins that are synthesized and
degraded throughout the cell cycle.
So, for example, cyclin E is synthesized
in G1 and degraded in S phase.
Cyclin A is synthesized in S phase and
degraded in the middle of mitosis and
cyclin B is synthesized at the end of S
phase and has to be degraded at the end
of mitosis in order for the cells
to be able to exit the cell cycle.