ABSTRACT
Stem cells, which regenerate tissue by producing differentiating cells, also produce cells that renew the stem cell population. Signals from regulatory microenvironments (niches) are thought to cause stem cells to retain self-renewing potential. However, the molecular characterization of niches remains an important goal. In Drosophila testes, germ line and somatic stem cells attach to a cluster of support cells called the hub. The hub specifically expresses Unpaired, a ligand activating the JAK-STAT (Janus kinase-signal transducer and activator of transcription) signaling cascade. Without JAK-STAT signaling, germ line stem cells differentiate but do not self-renew. Conversely, ectopic JAK-STAT signaling greatly expands both stem cell populations. We conclude that the support cells of the hub signal to adjacent stem cells by activation of the JAK-STAT pathway, thereby defining a niche for stem cell self-renewal.
Subject(s)
DNA-Binding Proteins/metabolism , Drosophila Proteins/metabolism , Drosophila/physiology , Germ Cells/physiology , Glycoproteins/metabolism , Protein-Tyrosine Kinases/metabolism , Stem Cells/physiology , Trans-Activators/metabolism , Transcription Factors , Animals , Cell Differentiation , Cell Lineage , Cell Survival , Contractile Proteins/analysis , DNA-Binding Proteins/genetics , Drosophila/cytology , Drosophila/genetics , Drosophila Proteins/genetics , Gene Expression , Germ Cells/cytology , Glycoproteins/genetics , Insect Proteins/genetics , Insect Proteins/metabolism , Janus Kinases , Ligands , Male , Microscopy, Confocal , Mutation , Protein-Tyrosine Kinases/genetics , STAT Transcription Factors , Signal Transduction , Spermatogenesis , Spermatogonia/physiology , Stem Cells/cytology , Testis/cytology , Testis/metabolism , Trans-Activators/geneticsABSTRACT
Novel candidate tumor suppressor p33ING1 is known to regulate activity of the p53 protein. The effect of p33ING1 inactivation on the functioning of the cell cycle "checkpoints" and the frequency of chromosomal aberrations was examined. Transduction of the p33-GSEas genetic suppressor element, known to reduce the p53 activity, into p53-positive rat and human cells resulted in: (1) partial abolishment of ethylmetansulphonate- or colcemid-induced arrest of the G1-to-S transition in the G0-synchronized cultures; (2) abolishment of the block in the S phase by the DNA synthesis inhibitor, N-phosphonacetil-L-aspartate (PALA); (3) an increase of the number of spontaneous chromosomal breaks and sister-chromatid exchanges; (4) increased frequency of colchicine-induced polyploidy. Similar effects were observed upon transduction of the p53-GSE22 genetic suppressor element, known to reduce p53 transcriptional activity. Presumably, the effect of p33ING1 inactivation on the cell cycle checkpoints and genetic stability is associated with a decrease in p53 activity.
Subject(s)
Cell Cycle/genetics , Genes, Tumor Suppressor , Genome , Proteins/genetics , Animals , Aspartic Acid/analogs & derivatives , Aspartic Acid/pharmacology , Cell Cycle Proteins , DNA Replication/drug effects , DNA-Binding Proteins , Demecolcine/pharmacology , Ethyl Methanesulfonate/pharmacology , Humans , Inhibitor of Growth Protein 1 , Intracellular Signaling Peptides and Proteins , Nuclear Proteins , Phosphonoacetic Acid/analogs & derivatives , Phosphonoacetic Acid/pharmacology , Polyploidy , Rats , Sister Chromatid Exchange , Transduction, Genetic , Tumor Suppressor ProteinsABSTRACT
The strain B-1166 differs from the other strains of Bacillus thuringiensis ssp. finitimus because it has two crystal types with different localization in the sporulating cell, i.e., inside and outside of exosporium membrane. Two dissociants of the strain were obtained containing only one of the crystal types. The initial strain produces at least three various delta-endotoxins (Fin2, Fin3, and Fin5) differing from all other known entomocidal proteins; Fin2 and Fin3 are similar to each other but differ from Fin5. Both crystal types contain the same endotoxins (Fin2, Fin3, and Fin5). In the B-1166 strain the site of crystal deposition is not determined by their protein composition.
