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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Gene Review

stg  -  string

Drosophila melanogaster

 
 
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High impact information on stg

  • Here we describe a novel mitotic inhibitor that acts during Drosophila gastrulation to counteract String/Cdc25, specifically in the cells that invaginate to form the mesoderm [1].
  • We show that Tribbles acts by specifically inducing degradation of the CDC25 mitotic activators String and Twine via the proteosome pathway [2].
  • Genetic and biochemical studies have indicated that the cdc25 protein controls the entry into mitosis by triggering tyrosine dephosphorylation of the cdc2 protein kinase [3].
  • These observations indicate that the cdc25 protein can function as a tyrosine phosphatase in the absence of any other protein [3].
  • We show that the isolated cdc25 protein can catalyze dephosphorylation of several model phosphatase substrates, including p-nitrophenyl phosphate and two distinct tyrosine-phosphorylated peptides [3].
 

Biological context of stg

 

Anatomical context of stg

  • Of the different cell fates normally represented in the sensilla (i.e., sensory neuron, thecogen cell, trichogen cell, tormogen cell, glia cell), only the phenotype of sensory neurons is expressed morphologically in stg embryos, suggesting that the neuronal fate predominates over the fates of the nonneuronal accessory cells [8].
  • The differentiation of undivided cells in stg embryos is not restricted to the peripheral nervous system; in all types of tissues analyzed in this study (e.g., epidermis, intestine, muscle, CNS), precursor cells express characteristics normally exhibited by their progeny [8].
  • Retinal precursors anterior to the furrow lacking stg arrest in G(2) and fail to enter mitosis, while cells within the furrow accumulate high levels of cyclins A and B. Although G(2)-arrested cells initiate normal pattern formation, the absence of stg results in retinal patterning defects due to the recruitment of extra photoreceptor cells [9].
  • Drosophila cdc25 protein from two different expression systems activates inactive cyclin-p34cdc2 and induces M phase in Xenopus oocytes and egg extracts [10].
  • The early blastomeres, macromeres and teloblasts have steady levels of maternal cdc25 RNA throughout their cell cycles [11].
 

Associations of stg with chemical compounds

 

Regulatory relationships of stg

  • Analysis of the activity of String enhancer elements in follicle cells reveals the presence of an element that promotes expression of String until just before the onset of polyploidy in wild-type follicle cells but well beyond this stage in Notch mutant follicle cells [14].
 

Other interactions of stg

  • We report that the loss of cycA, rca1 or stg leads to a block in the division of GMC-1, however, this GMC-1 exclusively adopts an RP2 identity [15].
  • This library was introduced into S.pombe cdc2 and cdc25 mutants, and plasmids isolated carrying cDNAs that complement these mutations [16].
  • A screen for dominant suppressors of the rux eye phenotype led to the identification of mutations in cyclin A, string (cdc25), and new cell cycle genes [17].
  • However, cell-cycle progression is arrested in the mesoderm of gastrulating embryos despite a positive transcriptional string/cdc25 activation provided by the mesoderm-specific action of Twist [18].
  • Consistent with this, the cycle 14 G2-arrest of stg mutant embryos is rescued by the hfp mutant [19].

References

  1. A genetic link between morphogenesis and cell division during formation of the ventral furrow in Drosophila. Grosshans, J., Wieschaus, E. Cell (2000) [Pubmed]
  2. Tribbles coordinates mitosis and morphogenesis in Drosophila by regulating string/CDC25 proteolysis. Mata, J., Curado, S., Ephrussi, A., Rørth, P. Cell (2000) [Pubmed]
  3. The cdc25 protein contains an intrinsic phosphatase activity. Dunphy, W.G., Kumagai, A. Cell (1991) [Pubmed]
  4. Pointed and Tramtrack69 establish an EGFR-dependent transcriptional switch to regulate mitosis. Baonza, A., Murawsky, C.M., Travers, A.A., Freeman, M. Nat. Cell Biol. (2002) [Pubmed]
  5. Notch-dependent Fizzy-related/Hec1/Cdh1 expression is required for the mitotic-to-endocycle transition in Drosophila follicle cells. Schaeffer, V., Althauser, C., Shcherbata, H.R., Deng, W.M., Ruohola-Baker, H. Curr. Biol. (2004) [Pubmed]
  6. Induction of string rescues the neuroblast proliferation defect in trol mutant animals. Park, Y., Ng, C., Datta, S. Genesis (2003) [Pubmed]
  7. Distinct molecular mechanism regulate cell cycle timing at successive stages of Drosophila embryogenesis. Edgar, B.A., Sprenger, F., Duronio, R.J., Leopold, P., O'Farrell, P.H. Genes Dev. (1994) [Pubmed]
  8. Sensillum development in the absence of cell division: the sensillum phenotype of the Drosophila mutant string. Hartenstein, V., Posakony, J.W. Dev. Biol. (1990) [Pubmed]
  9. Pattern formation in the absence of cell proliferation: tissue-specific regulation of cell cycle progression by string (stg) during Drosophila eye development. Mozer, B.A., Easwarachandran, K. Dev. Biol. (1999) [Pubmed]
  10. cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2. Gautier, J., Solomon, M.J., Booher, R.N., Bazan, J.F., Kirschner, M.W. Cell (1991) [Pubmed]
  11. Expression of the cell cycle control gene, cdc25, is constitutive in the segmental founder cells but is cell-cycle-regulated in the micromeres of leech embryos. Bissen, S.T. Development (1995) [Pubmed]
  12. Cell cycle progression and cell division are sensitive to hypoxia in Drosophila melanogaster embryos. Douglas, R.M., Xu, T., Haddad, G.G. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2001) [Pubmed]
  13. p55CDC25 is a nuclear protein required for the initiation of mitosis in human cells. Millar, J.B., Blevitt, J., Gerace, L., Sadhu, K., Featherstone, C., Russell, P. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  14. Notch-Delta signaling induces a transition from mitotic cell cycle to endocycle in Drosophila follicle cells. Deng, W.M., Althauser, C., Ruohola-Baker, H. Development (2001) [Pubmed]
  15. Cell division genes promote asymmetric interaction between Numb and Notch in the Drosophila CNS. Wai, P., Truong, B., Bhat, K.M. Development (1999) [Pubmed]
  16. Complementation of fission yeast cdc2ts and cdc25ts mutants identifies two cell cycle genes from Drosophila: a cdc2 homologue and string. Jimenez, J., Alphey, L., Nurse, P., Glover, D.M. EMBO J. (1990) [Pubmed]
  17. Control of G1 in the developing Drosophila eye: rca1 regulates Cyclin A. Dong, X., Zavitz, K.H., Thomas, B.J., Lin, M., Campbell, S., Zipursky, S.L. Genes Dev. (1997) [Pubmed]
  18. Cell divisions in the drosophila embryonic mesoderm are repressed via posttranscriptional regulation of string/cdc25 by HOW. Nabel-Rosen, H., Toledano-Katchalski, H., Volohonsky, G., Volk, T. Curr. Biol. (2005) [Pubmed]
  19. Drosophila Hfp negatively regulates dmyc and stg to inhibit cell proliferation. Quinn, L.M., Dickins, R.A., Coombe, M., Hime, G.R., Bowtell, D.D., Richardson, H. Development (2004) [Pubmed]
 
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