Regulationofcellproliferationandcancercells细胞增殖调控与癌细胞.pptVIP

M-cyclin inactivion: control of proteolysis by Cdc20-APC. Cell exists from mitosis Children with Down syndrome. The disease is caused by trisomy 21, meaning their bodies cells have an extra chromosome 21 4. G1 checkpoint Mechanisms controlling cell-cycle entry and S-phase initiation in animal cells The Rb proteins itself was identified originally through studies an inherited eye cancer in children, retinoblastoma. 5. The diversity of cyclin-Cdk complex G1-cyclins: 促使细胞通过G1checkpoint G1/S-cyclins: 在G1末结合Cdks促使细胞 DNA复制 S-cyclins: 结合S-Cdk启动DNA复制 M-cyclins: 促使细胞进入mitosis Cyclin-Cdk Vertebrates Budding Yeast G1 cyclinD Cdk4,6 Cln3 Cdk1 G1/S cyclinE Cdk2 Cln1,2 Cdk1 S cyclinA Cdk2 Clb5,6 Cdk1 M cyclinB Cdk1 Clb1,2,3,4 Cdk1 Cdk1: cdc2 in vertebrates and fission yeast, cdc28 in budding yeast Various cyclin-Cdk complexes are regulated by: 在不同时相各种Cyclins的合成与降解 Cyclin-Cdk 复合物被不同Kinase和Phosphatase作用 6. Inhibition of cell cycle progression Binding of Cdk inhibitor proteins (CKIs/ CDIs) Turn off cyclin and Cdk gene expression DNA damage and p53 DNA damage checkpoints: in late G1 or in late G2 Inhibiting G1/S and S cyclin-Cdk complex Ubiquitin ligase Dasgupta et al., Proc. Nat’l Acad. Sci. USA, 2006, 103: 6332-6337 What happens if DNA damage is so severe that repair is not possible? Unicellular organisms Multicellular organisms DNA damage--p53--apoptosis If the DNA damage cannot repaired, p53 activates the transcription of genes that trigger cell death via apoptosis p53: Guardian of the genome Cell and Molecular Biology (? John Wiley Sons 2010) The protein kinases Chk1 and Chk2 also block cell cycle progression by phosphorylation of Cdc25 family. Degradation in a Ubiquitin-proteasome dependent pathway DNA damage Chk1 Chk2 ATM/ATR CDC25A CyclinE, A/Cdk2 本课程所用的一些素材为主讲教师多年的教学积累，来源于