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

• This 'second mitotic wave' is triggered by EGFR signalling and depends on expression of String, the Drosophila homologue of Cdc25 phosphatase, the ultimate regulator of mitosis in all eukaryotic cells [4].
• In this context, the only known cell cycle component that responds to the Notch pathway is String/Cdc25 (Stg), a G2/M cell cycle regulator [5].
• These results suggest that Drosophila Cdc25 may directly or indirectly increase the kinase activity of Cyclin E-Cdk2 complexes in vivo, thus driving arrested neuroblasts into cell division [6].
• During interphase 14, programmed degradation of maternal String protein leads to inhibitory phosphorylation of Cdc2 and cell cycle arrest [7].
• The conserved regulators of cell cycle progression--Cyclins, Cdc2 kinase, and String phosphatase (Cdc25)--accommodate multiple modes of regulation during Drosophila embryogenesis [7].

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

• Moreover, the phosphatase activity of the cdc25 protein is eliminated by treatment with N-ethylmaleimide or by alteration of a single conserved cysteine residue by site-directed mutagenesis [3].
• Immunoblot analysis of embryos whose cell divisions are synchronized by inducible String (cdc25 homolog) demonstrated that cyclin B was degraded during low O2 conditions in interphase-arrested embryos but not in those arrested in metaphase [12].
• Therefore, cdc25 is a specific protein phosphatase that dephosphorylates tyrosine and possibly threonine residues on p34cdc2 and regulates MPF activation [10].
• The cdc25+ gene of fission yeast encodes a phosphotyrosine phosphatase that dephosphorylates tyrosine-15 of p34cdc2 and thereby activates p34cdc2/cyclin to bring about entry into M phase [13].

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