第14章细胞增殖调控与癌细胞

Amphibian oocytes and early embryos of frogs
(引自翟中和等，2011)
Masui and Markert’s experiments (J. Exp. Zool. 1971, 177: 142)
What’s the role of hormone? Trigger protein synthesis
In most eucaryotic cells, the cell-cycle control system triggers cell-cycle progression at three major regulatory transitions, or checkpoints
(From the World of the Cell, 2000)
Cdc2
MPF has protein kinase activity
cyclin
M phase Cyclin-Cdk (MPF) (Cyclin-dependent protein kinase)
cyclin-dependent kinase (Cdk)
MPF的发现
• HeLa细胞融合：有丝分裂促进因子
Regulation of cell proliferation
and canHale Waihona Puke Baiduer cells
细胞增殖调控与癌细胞
Section 1 Regulation of Cell Proliferation
1. Cell-cycle control system
and Checkpoints
Cell-cycle control system safely guides the cell through the events of the cell cycle
• The wee2 gene was later
（University of Oxford）
renamed cell division cycle 2
(CDC2 is identical in function to
CDC28 from budding yeast 1982).
cdc2D
Normal
35S-Met: Fertilized eggs
16 min 60 min 85 min 120 min
Samples after fertilized
Cyclin: in sea urchin eggs that is destroyed at each cleavage division.
Cell, 1983, 33:389-396
Interphase Interphase High Low
➢Tim Hunt found cyclin in 1983: sea urchin eggs
When the gel was developed on Friday 23 July 1982, I found that the strongest band early on suddenly got very much weaker at about the time when the eggs were about to divide in two. This was a stunning, startling discovery.“
• 非洲爪蟾卵细胞提取物注射：MPF概念提 出
• 酵母温度敏感突变株：cdc基因，p34cdc2， Cdc28
• 海胆卵细胞：Cyclin的发现 •thMe P20F0生1 N化o成be分l P：rizCedfoc2r P和hyCsiyocloligny or Medicine
(2) Activation of MPF
By cyclin
mitosis
mitosis
Cyclin concentration
interphase
interphase
By phosphatase and Kinase
cdc2-
Cdc2 encodes a protein kinase with 34kD whose activity is required for cells to enter M phase.(p34cdc2)
Hartwell found cdc28
• What is the relationship between cyclins or cdc2 and MPF? MPF purification: 1988 (Xenopus egg) MPF=32kD+45kD Cyclin B Cdc2
(1) Discovery Does the cytoplasm of cells contain regulatory factors that affect cell cycle activities?
(引自翟中和等，2011)
M phase HeLa cell with a rat kangaroo PtK2 cell, 1974, Humangenetik
➢Nurse found cdc2
• In the mid-1970s as a postdoc studying the fission yeast S. pombe.
• Divide before they had reached full size: Mutants – wee:
Wee1，wee2
(引自翟中和等，2011)
1978, MPF activity undergoes dramatic fluctuations in cleaving eggs that correlate with changes in the cell cycle
Mitosis
Mitosis
Mitosis
MPF activity
Cell-cycle control system: cyclically activated protein kinases
2. MPF: transition from G2 to M
Maturation-promoting factor / Mitosis-promoting factor