Cell Cycle Control

Transforming growth factor (3 (TGF(3) (that suppresses cell proliferation), the related develop-mentally important activins (involved in mesoderm induction) and bone morphogenetic proteins (involved in bone formation) act via PM-located transmembrane receptors that are Ser/Thr-specific PKs. Thus, TGF(3 binds to the extracellular domain of a specific TGF(3 receptor with the successive consequences of activation of the receptor Ser/Thr-specific PK activity, phosphorylation of a protein Mad to yield P-Mad and downstream consequences resulting in developmentally important specific gene expression. Thus, dorso-ventral differentiation in Xenopus embryos involves Mad-like proteins and a Mad-like gene is a tumour suppressor gene. 

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Cell Cycle Control. Figure 1 Cell cycle regulation by Cyclin dependent kinases (CDKs). Different cyclins bound to different CDKs promote the transition from one cell cycle phase into another. CDK-dependent phosphorylation of Rb is required to release active E2F transcription factors, which promotes entry into S phase. 

Cell Cycle Control. Figure 3 The DNA damage checkpoint. In response to DNA damage cells activate p53 dependent and independent checkpoint pathways leading to cell cycle arrest at G1/S and G2/M allowing DNA repair. If the cellular damage cannot be repaired, cells can initiate apoptosis. 

Cell Cycle Control Diabetes Mellitus Retinoids... 

Since the SUMO pathway affects multiple pathways ranging from transcription, DNA repair, and intracellular trafficking over cell signaling and cell cycle control to basic metabolism, it is not suiprising that links to diseases and viral assaults are emerging. However, the field is not yet at a stage sufficiently developed for pharmacological intervention. Below we will describe selected examples for links of the SUMO pathway to diseases and viral functions. 

Cell Adhesion Molecules Cell-cycle Arrest Cell Cycle Checkpoints Cell Cycle Control Cell Division Cycle Cell Multiplication Cell Proliferation Cellular Immmunity Central Core Disease (CCD)... 

Hartwell LH, Kastan MB Cell cycle control and cancer. Science 1994 266 1821. 

Booher, R., and Beach, D. (1986). Site-specific mutagenesis of cdc2+, a cell cycle control gene of the fission yeast Schizosaccaromyces pombe. Mol. Cell. Biol. 6 3523-3530. Booher, R. N., Alfa, C. E., Hyams, J. S., and Beach, D. H. (1989). The fission yeast cdc2/cdcl3/sucl protein kinase regulation of catalytic activity and nuclear localization. CeU 58 485-497. 

Boulton, T. G., Yancopoulos, G. D., Gregory, J. S., Slaughter, C., Moomaw, C., Hsu, J., and Cobb, M. H. (1990). An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control. Science 249 64-67. 

D Urso, G., Marraccino, R. L., Marshak, D. R., and Roberts, J. M. (1990). Cell cycle control of DNA replication by a homologue from human cells of the p34cprotein kinase. Science 250 786-791. 

Enoch, T and Nurse, P. (1990). Mutation of the fission yeast cell cycle control genes abolishes dependence of mitosis on DNA replication. Cell 60 665-673. 

Gautier, J., Norbury, C., Lohka, M., Nurse, P., and Mailer, J. (1988). Purified maturation-promoting factor contains the product of a Xenopus homologue of the fission yeast cell cycle control gene cdc2+. Cell 54 433-439. 

Simanis, V., and Nurse, R (1986). The cell cycle control gene cdc2+ of fission yeast encodes a protein kinase potentially regulated by phosphorylation. Cell 45 261-268. 

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