Abnormal Cell Proliferation,Differentiation Apoptosis and Related of Disease

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??????????????? Abnormal Cell Proliferation,Diffe
rentiation Apoptosis and Related of Disease
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????????? Abnormal Cell Proliferation and
Diseases ?????????? ???????( Concept
and phases of Cell cycle) ?Cell
Proliferation? ??????????,??????????,???? ??
???,?????????????
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1. ????????(Regulation of intracellular signals )
???????????????????????? (Cyclin dependent
kinase, CDKs)
Key spotCyclin? CDKs? CDI?Checkpoint of cell
cycle?
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??????
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?CDK1????cell cycle?
CDK????(CDK activation kinase CAK)
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?CDI CDI??????CDK???? ?Ink4P16INK4a?P15INK4b?P18I
NK4c?P19INK4d CDK4?CDK6 ?Cip/Kipp
21Cipl?P27Kip1?P57Kip1 CDK2
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??????
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??????
????(TGF-ß)
????cyclin?CDK4??????P21wafl?P27kipl?P15ink4b?CDI?
?,??????G1??
?????????
??P16INK4a?P15INK4b??,?????Cyclin
D-CDK4/6??????,????G1??
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???? ????????
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1.?????????? Cyclins????(Overexpre
ssion of cyclins) ??????cyclin(D?E)?????
?? ?Cyclin D1(Bcl-1)??????(????)
?????(Cyclin D1????????)
????????????Cyclin D1???????
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??????
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??????
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??????
DNA?? SV40?HPV????? P53????
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?????????(PT)
???????
???
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?????????(Regulation, Differentiation)
??????(Concept) ??????,?????????????
???????????
2.?????? ???? ???? ???? ???????????
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2. ?????????????
?????????,?????????,???????? ????(??????)??,??????
????
3. ??????? ?????????????????????????
??? ???????????????,???????????????
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?The regulation of cell differentiation
1. ??????(Regulation on the genomic level)
House-keeping genes(????????)
House-keeping genes generally encode proteins
that participate in basic or universal cellular
functions essential for maintaining cell
survival. ??????(?????????)
2. ???????? (Regulation on
transcription and post- transcription levels)
??????(?????????????????)
???????(?mRNA????????iRNA??)
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??????
3. ?????????? 4. ???????
(Extracellular factors that control
differentiation) ??????????????????????????
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?Abnormal differentiation diseases 1.
??(Tumor) Hallmark of cancers differentiation
????????????
???? ???????????,?????? ???????????????
???????? (Mechanism of deregulation
differentiation) ????????????
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??????
?????????? ??????????????

?????????? ??????AFP???????A?
????CEA???
?????????????? ??????????????????????????
????????????????????????? ?????????????,?????????
??? ?????????,????????????
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(?)??????(The process of apoptosis)
??????
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????(????)???????? ?????(Blebbing) ????(Condens
ation)??????? ????(Apoptotic small body)
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1. Caspase???????(Caspase-independent
apoptosis) (1) Concept, Classification,
Construction of Caspases ??Caspase???????????,1
4????
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c-FLIP cellular Fas-associated death domain-like
IL-1 beta-converting enzyme inhibitory protein
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(2)??????(Extrinsic or cytoplasmic pathway) ????
TNFR?FasR?DR3?DR4?DR5? ????????????,??????
????????? ??(pathway)
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2.?Caspase??????????? ???
??Ca/Mg2????????,??DNA?? ??????????????????????
?,??????????? ??????(AIF)
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??????
?????????
TNF-a??CD3???TCDD?
??Ca2 ?
??Ca2/Mg2????????,??DNA? ?????????,??????????
??????,?? ??????? ???????,????????????? ?AT
P???,????????????,???DNA???? ?DNA?
????
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???????????(Mechanism of apoptosis
) 1.????(Oxidation damage ) ??????????????/??????,
????? ???????,???????????? ?Mechanism? ??p53?????A
TP??????????????? ??,??????? ?????????????????????
??? 2.???(Calcium overload ) 3.?????(
Mitochondria damage )
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??????
???????????
(Regulated mechanism of apoptosis)
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Bcl-2(Bcl-XL)???????MPT??,Cyt.c ?AIF???
Bcl-2???????Apaf-1,???caspase-9??
Bcl-2???????????C
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??????? P53???Bcl-2??????,??Bcl-2????
P53????????????(??????????)? P53?????????????(Ba
x?NOXA? PUMA)? ?,???????C???caspase???
P53??????Fas??? P53???????????????
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??????
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(?)??????(Apoptosis inhibition) 1. ??(Tumor)
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?????????????????,????????????
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2.?????(Autoimmune diseases) ?????????????????,???
????? ?????????????,?????????
(?)??????(Apoptosis excess) 1.???????-????? ?? ??
????????,??????????? ?????????????,?????????? ???
???????,????????? ?? ???????FasR????p53????????
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PEST ?????C-??????(?????)??Pro(P), Glu(E),
Ser(S)?Thr(T)???(???(P),???(E),??? (S),????(T)??)
?40?aa????????,? ?PEST??,?????????????? ? PEST
????3 ?????????????????,? 3???????????,ste3p
?????????????
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