????(cell proliferation)????????????????????????,??????????????,???????????????????????????????????????

1
???? ????????
2

• ????(cell proliferation)?????????????????
  ???????,??????????????,???????????????????????????
  ????????????

3
??? ??????
4
??????

• ????????????????????????????????????????????
  
• ??????,????????????????????????

5
(No Transcript)
6
?????????

• ???(interphase)??????????????????
• G1?(Gap1 phase)?M????S??????????
• S?DNA???(DNA synthetic phase)
• G2?(Gap2 phase)DNA???(S?),????????????
• ?M??????(mitosis phase)?

7
Phases of the cell cycle
8
?????????
?cycling cell(????????????) ?????????????????
???? ?quiescent cell(??????G0???)
???????????????? ?????,???????,???
??????????????
9
?????????
??????(synchronization) ?????? ?????? ??????(sele
ction synchrony) ???????? ???????? ?????? ?DNA????
? ???????? ?????(conditional mutants)
10
?? ?????????????????

• ?G1? (Gap1 phase)
• ?S ?(synthesis phase)
• ?G2 ?(Gap2 phase)
• ? M?

11
G1? (Gap1 phase)
??????,????rRNA? ?????????,?G1???, DNA????
???????
12
S ? (synthesis phase)
DNA??,??????????DNA???????
????????,?????? GC????DNA?????AT???? ???
13
G2?(Gap2 phase)
????ATP?RNA????, ????????????(maturation
promoting factor,MPF)
14
???????(Cell Cycle Checkpoints)
????????????
?G1??(??G1??) ?G2??(?G2????) ?????(????)
??????,?????????????????????????????
15
Cell Cycle Checkpoints
16
G1??(START????)

• ?G1??(?????START,????????????commitment
  point),???????????????
• ?G1?????????????,???????????

17
G2??
?G2??????????????? ????????DNA????????G2?????
????????DNA, ?????????????? ???
DNA????,G2?????? ????,??????M??
18
????
???????????????? ??,?????????????? MPF???
?,????????????????
19
??? ???????

• ???????????????????????,?????????????,??
  ???????????

20
??MPF???????

• 1970s Rao?Johnson???M???(Hela)??????????????,????
  ????????? (prematurely condensed chromosome,PCC)?
• G1?PCC????,?DNA????
• S?PCC????,?DNA??????????
• G2?PCC??????,??DNA??????

21
G1????M?????
22
S????M?????
23
G2????M?????
24

• ??????M???????PCC??,??M??????????????????,???????
  (maturation promoting factor, MPF)?

25
??????????
26

• 1988?Lohka??????MPF??????MPF?32KD?45KD??????,????
  ??/??????

27
??p34cdc2????????MPF???

• 1960s Leland Hartwell,1970s Paul Nurse
  ???????????????,?????????,??????????????(cell
  division cycle gene, cdc)?
• ????cdc2? ????cdc28?????????????
• cdc2?cdc28?????34KD?????(p34cdc2 ),??????????
• p34cdc2 ?p34cdc28??????????,??????????????????

28

• p34cdc2?MPF???
• James Maller ????Paul Nurse???????MPF??p32???p3
  4cdc2???????,??p34cdc2????????MPF??,?????????

29
??????

• 1980s Timothy Hunt?????????????????????????,?????
  ??(cyclin A?B)??????????????????mRNA??????????
• ????????MPFcdc2clyclin B

30

• ?MPF?????
• ??????????????????
• ?????
• ?????/????????
• ???????????,??????????????(cyclin-dependent
  protein kinases,Cdks)
• ?????????(cyclin)?

31
MPF???
32
2001?10?8????Leland Hartwell????Paul
Nurse?Timothy Hunt????????????????????????
Leland H. Hartwell
R. Timothy (Tim) Hunt
Sir Paul M. Nurse
33
??????cyclin

• ????????????????????100?????????,???????,???????C
  DK???
• ????CDK,??CDK????????
• ??30??,???????A1-2?B1-3 ?C? D1-3?E1-2?F?G?H??
• ??4?G1??G1/S??S??M??

34
?????CDK/cyclin???

• ??D1-3,???cyclin D????????????,?????????

35
??????????????

• ?????????????????CDK???
• ??
• M?????????N??????(?9??????),????????????A?B????
• G1?????????????,??C????????PEST??,???G1??????????
  ?

36
??????????

• G1?,?????????,cyclin D??,??CDK4?CDK6??,????????Rb?
  ??,Rb???????E2F,?????????,???cyclinE?A?CDK1????
• G1-S?,cyclinE?CDK2??,??????S??CyclinE??????????G1?
  ?
• ?G2-M?,cyclinA?cyclinB?CDK1??,CDK1??????????????H1
  ??????????,??????????????

37

• cell cycle regulation

38

• ????MPF???????,????????APC,??????cyclinB?,cycl
  inB?????(proteasome)??,?????????
• ???????N????????????,????(destruction box)?
• ???76??????,??????????????????????????,???????????
  ??????????????
• 26S?????????????,???????????????

39
Destruction Box in Cyclins
40
(No Transcript)
41
(No Transcript)
42
M?CDK???

• M?CDK?????????cyclin????
• ??cyclin B?CDK1?Wee1?Thr14?Tyr15?????????,?CDK/cy
  clin?????
• ?M?,Wee1?????,CDC25?CDK????,???CDK??????
• CDK?????Thr161????,???CDK??(CDK activating
  kinase CAK)????????

43
CDK activating
44
??

• ??????
• 1.????
• 2.????
• 3.MPF
• 4.????
• 5.CDK??
• ?????
• 1.????????????????????
• 2.?????????????,??????