1. Chapter8(2) Abnormal cell proliferation, differentiation and related diseases

2. What is cell proliferation? Cell proliferation is a process of cell division and regeneration, which results in an increase in the cell number with exact passages of genetic information to their daughter cells.

3. Proliferation of eukaryotic cell Cell growth DNA replication Cell division What is cell cycle? Cell cycle is defined as a period from the end of one division to the beginning of next division of a proliferative cell.

4. Phases of the cell cycle G1 phase S phase G2 phase M phase

5. Phases of the cell cycle DNA Cell Cycle Analysis G1 phase S phase G2 phase M phase

6. For adult Cycling cells with continuous division Embryo cells, hematopoietic cells Differentiated cells Cardiac cells, nerve cells Most cells Skin fibroblasts, SMCs, VECs, cells of internal organs

7. Control of the Cell Cycle Cyclins Cdks (Cyclin-dependent kinases) CKIs(Cyclin dependent kinase inhibitor ) APC (anaphase-promoting complex) The passage of a cell through the cell cycle is controlled by proteins in the cytoplasm. These protein are:

8. Control of the Cell Cycle Cyclins Cdks (Cyclin-dependent kinases) CKIs(Cyclin dependent kinase inhibitor ) APC (anaphase-promoting complex) The passage of a cell through the cell cycle is controlled by proteins in the cytoplasm. These protein are:

9. Cyclins Kinase complex VertebrateYeast CyclinCDKCyclinCDK G 1 -CDKCyclin D* CDK4 、 6 Cln 3CDK1(CDC28) G 1 /S-CDKCyclin ECDK2 Cln 1 、 2 CDK1(CDC28) S-CDKCyclin ACDK2 Clb 5 、 6 CDK1(CDC28) M-CDKCyclin BCDK1(CDC2)Clb 1-4CDK1(CDC28)

10. Cyclins Kinase complex VertebrateYeast CyclinCDKCyclinCDK G 1 -CDKCyclin D* CDK4 、 6 Cln 3CDK1(CDC28) G 1 /S-CDKCyclin ECDK2 Cln 1 、 2 CDK1(CDC28) S-CDKCyclin ACDK2 Clb 5 、 6 CDK1(CDC28) M-CDKCyclin BCDK1(CDC2)Clb 1-4CDK1(CDC28)

11. Cyclins Kinase complex VertebrateYeast CyclinCDKCyclinCDK G 1 -CDKCyclin D* CDK4 、 6 Cln 3CDK1(CDC28) G 1 /S-CDKCyclin ECDK2 Cln 1 、 2 CDK1(CDC28) S-CDKCyclin ACDK2 Clb 5 、 6 CDK1(CDC28) M-CDKCyclin BCDK1(CDC2)Clb 1-4CDK1(CDC28)

12. Cdks Kinase complex VertebrateYeast CyclinCDKCyclinCDK G 1 -CDKCyclin D* CDK4 、 6 Cln 3CDK1(CDC28) G 1 /S-CDKCyclin ECDK2 Cln 1 、 2 CDK1(CDC28) S-CDKCyclin ACDK2 Clb 5 、 6 CDK1(CDC28) M-CDKCyclin BCDK1(CDC 2) Clb 1-4CDK1(CDC28)

13. Cdks

14. Steps in the cycle

15. CKIs Kip (Kinase inhibition protein) ： P21 waf1/cip1 (cyclin inhibition protein 1) 、 P27 kip1 (kinase inhibition protein 1) 、 P57 kip2 Ink4(Inhibitor of cdk 4): P16 Ink4a 、 P15 Ink4b P18 Ink4c 、 P19 Ink4d

16. CKIs Kip (Kinase inhibition protein) ： P21 waf1/cip1 (cyclin inhibition protein 1) 、 P27 kip1 (kinase inhibition protein 1) 、 P57 kip2 Ink4(Inhibitor of cdk 4): P16 Ink4a 、 P15 Ink4b P18 Ink4c 、 P19 Ink4d

17. Degradation of cyclin B

19. Cell cycle checkpoints

20. Regulation of cell cycle by extracellular signal Growth factors

21. Tumor Overexpression of cyclins Overexpression of Cdks Deactivation of CkIs Abnormity of checkpoints

22. Tumor Overexpression of cyclins Overexpression of Cdks Deactivation of CkIs Abnormity of checkpoints

23. Psoriasis

24. What is cell differentiation? Cell differentiation is a cellular events that gives rise to different kinds of cells with the specialized morphology, metabolism and physiological functions from the cells of the same origin.

25. What is cell differentiation?

26. Cell differentiation is a cellular events that gives rise to different kinds of cells with the specialized morphology, metabolism and physiological functions from the cells of the same origin.

27. Control of cell differentiation –Genomic level –Transcription/post-transcription levels –Extracellular factors

28. Differentiation-related genes House-keeping genes Tissue-specific genes DNA methylation↓ DNA methylation↓

29. Control of cell differentiation –Genomic level –Transcription/post-transcription levels –Extracellular factors

30. Tumor Low differentiation Dedifferentiation Retrodifferentiation Divergent differentiation Induced differentiation

31. Pulmonary fibrosis Thrombin Myofibroblast Fibroblast Vessel injury Deposit of collagen in lung (+)(+)

32. Teratoma