The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)
-
date post
19-Dec-2015 -
Category
Documents
-
view
220 -
download
2
Transcript of The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)
![Page 1: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/1.jpg)
The Hallmarks of Cancer
Hanahan and Weinberg, Cell 100:57-70 (2000)
![Page 2: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/2.jpg)
Cell Regulatory Networks Important in Cancer Cells
Hanahan and Weinberg, Cell 100:57-70 (2000)
![Page 3: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/3.jpg)
Figure 8.3b The Biology of Cancer (© Garland Science 2007)
STARTor
Restriction Point
![Page 4: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/4.jpg)
Figure 8.1 The Biology of Cancer (© Garland Science 2007)
![Page 5: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/5.jpg)
Figure 8.6 The Biology of Cancer (© Garland Science 2007)
![Page 6: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/6.jpg)
The Main Jobs of the Cell Cycle:
1. To accurately transmit the genetic information!
2. To maintain normal ploidy; i.e. diploidy!
Euploidy: additions of whole chromosome setse.g. n, 2n, 3n, 4n = haploid, diploid, triploid, tetraploid
Aneuploidy: additions or subtractions of one or more single chromosomese.g. 2n + 1, 2n -1, 2n + 2, etc.
![Page 7: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/7.jpg)
Figure 8.4 The Biology of Cancer (© Garland Science 2007)
![Page 8: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/8.jpg)
Properties Required for Transmission of Chromosomes During Cell Division
1. One and only one centromere
2. Functional telomere at both ends
3. Chromosomes must be fully replicated
4. Chromosomes cannot be too large or too small
![Page 9: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/9.jpg)
S Phase of the Cell Cycle
![Page 10: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/10.jpg)
Mitosis
![Page 11: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/11.jpg)
Mitosis in an Early Fruit Fly Embryo
![Page 12: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/12.jpg)
Figure 8.3a The Biology of Cancer (© Garland Science 2007)
Mitosis in NewtLung Cells
blue = DNAgreen = microtubules
![Page 13: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/13.jpg)
Metaphase in a mammalian cell
![Page 14: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/14.jpg)
![Page 15: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/15.jpg)
Anaphase in a plant cell
![Page 16: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/16.jpg)
G1-S and G2-M are the major control points in the cell cycle
Rao and Johnsoncell fusion experiments
1. Fuse M phase cell with interphase cell: Interphase nucleus enters M
2. Fuse S phase cell with G1 cell: The G1 nucleus enters S phase
3. Fuse S phase cell with G2 cell: The G2 nucleus does not enter S phase
![Page 17: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/17.jpg)
Cyclin Dependent Kinases Regulate the Cell Cycle
![Page 18: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/18.jpg)
Experimental Systems Important for Cell Cycle Studies
Arbacia punctulata
Xenopus laevisSchizosaccharomyces pombe
Saccharomyces cerevisiae
![Page 19: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/19.jpg)
Fission yeast: Schizosaccharomyces pombe
![Page 20: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/20.jpg)
Budding Yeast Saccharomyces cerevisiae
![Page 21: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/21.jpg)
Isolating Temperature Sensitive Mutants in Haploid Yeast
![Page 22: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/22.jpg)
Permissive (low) temperature Restrictive (high) temperature
Cdc Mutants Arrest at the Same Cell Cycle Phase
![Page 23: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/23.jpg)
Phosphorylation of CDK Targets Changes Their Activity
Now performsa cell cycle function
![Page 24: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/24.jpg)
cdc mutant growingat permissive temp (23C)
cdc mutant growth arrested after 6 hrs at non-permissive temp (36C)
The Behavior of a Temperature Sensitive cdc Mutant
![Page 25: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/25.jpg)
How to Clone cdc Genes in Yeast
![Page 26: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/26.jpg)
Cdc Genes Encode Proteins Needed for DNA ReplicationStudies in S. cerevisiae
![Page 27: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/27.jpg)
Cdc Genes Encode Proteins Needed for the G2-M Transition:Studies in S. pombe
cdc2+ encodes a kinase Moreover = cdc28 in S. cerevisiae!
![Page 28: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/28.jpg)
Cyclin was Discovered in Sea Urchin Embryos
ProteinLevel
Time
cyclin A cyclin B
M M M
can stimulate to
lay lots of eggs
![Page 29: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/29.jpg)
mitosis mitosis mitosis
(Spisula is actually a clam.)
![Page 30: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/30.jpg)
Overview of the frog life cycle
1 mm
spermtadpole feeds, grows
and becomes an adult frog
OOCYTE GROWS WITHOUT DIVIDING(MONTHS) FERTILIZATION
FERTILIZED EGG DIVIDES WITHOUT GROWING(HOURS)
![Page 31: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/31.jpg)
The Maturation of Frog Eggs
![Page 32: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/32.jpg)
The Maturation of Frog Eggs
An Assay for Maturation Promoting Factor (MPF)
Yoshio Masui, 1971
![Page 33: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/33.jpg)
MPF Activity Peaks Before Each Cell Division
Moreover, MPF has kinase activity
![Page 34: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/34.jpg)
![Page 35: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/35.jpg)
Purification of MPF: The Birthof Cyclin Dependent Kinases
This is cdc2+!!(Cdc28 in
S. cerevisiae)
This is cyclin!!
Which = cdc13+
in S. pombe
![Page 36: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/36.jpg)
Phosphorylation of CDK Targets Changes Their Activity
Now performsa cell cycle function
![Page 37: The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649d2b5503460f94a013f3/html5/thumbnails/37.jpg)
The Nobel Prize in Physiology or Medicine, 2001
“for their discovery of key regulators of the cell cycle”