Bunched, the Drosophila homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth

<p>Abstract</p> <p>Background</p> <p>Transforming Growth Factor-β1 stimulated clone-22 (TSC-22) is assumed to act as a negative growth regulator and tumor suppressor. TSC-22 belongs to a family of putative transcription factors encoded by four distinct loci in mammals. Possible redundancy among the members of the TSC-22/Dip/Bun protein family complicates a genetic analysis. In <it>Drosophila</it>, all proteins homologous to the TSC-22/Dip/Bun family members are derived from a single locus called <it>bunched </it>(<it>bun</it>).</p> <p>Results</p> <p>We have identified <it>bun </it>in an unbiased genetic screen for growth regulators in <it>Drosophila</it>. Rather unexpectedly, <it>bun </it>mutations result in a growth deficit. Under standard conditions, only the long protein isoform BunA – but not the short isoforms BunB and BunC – is essential and affects growth. Whereas reducing <it>bunA </it>function diminishes cell number and cell size, overexpression of the short isoforms BunB and BunC antagonizes <it>bunA </it>function.</p> <p>Conclusion</p> <p>Our findings establish a growth-promoting function of <it>Drosophila </it>BunA. Since the published studies on mammalian systems have largely neglected the long TSC-22 protein version, we hypothesize that the long TSC-22 protein is a functional homolog of BunA in growth regulation, and that it is antagonized by the short TSC-22 protein.</p

ConPaaS: an Integrated Runtime Environment for Elastic Cloud Applications

Most Cloud applications are re-enactments of traditional enterprise applications such as Web applications, content delivery and e-commerce [1]. The advantages of the Cloud are well-known: access to a near-infinite number of resources

Bunched, the homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth-2

<p><b>Copyright information:</b></p><p>Taken from "Bunched, the homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth"</p><p>http://www.biomedcentral.com/1471-213X/8/10</p><p>BMC Developmental Biology 2008;8():10-10.</p><p>Published online 28 Jan 2008</p><p>PMCID:PMC2253523.</p><p></p> homozygous mutant cells (black) and its wild-type sister clone (bright green) were induced by the FLP/FRT recombination system (genotype , heat shock for 25 min at 34°C 24–48 h AED), and larvae were dissected 51–52 h after induction of mitotic recombination. (B) Nuclei are visualized by DAPI staining. (D-E) Statistical analyses of twin-spot clones (= 12 for every genotype). Control clones () contain roughly the same number of cells (38 ± 7) as their sister clones (39 ± 13) and cover a comparable area (4291 ± 1506 and 4471 ± 1976 pixels, respectively; data points are evenly distributed around the straight line with the slope m = 1). However, cell number and clone area are reduced in mutant clones (shift of data points). Homozygous mutant and clones contain significantly (≤ 0.05) fewer cells (30 ± 11 and 30 ± 8, respectively) than their sister clones (40 ± 13 and 37 ± 11, respectively). The areas covered by and mutant clones (3424 ± 1256 and 2826 ± 1216 pixels, respectively) are smaller than the areas covered by their sister clones (4785 ± 1516 and 3903 ± 1939 pixels, respectively; = 0.013 and = 0.06). The effect on clone area is slightly more pronounced than the effect on cell number, indicating a decrease in size of mutant cells. (F) The average area of the mutant cells is 5% () and 10% () smaller than the average area of the wild-type sister cells

Bunched, the homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth-4

<p><b>Copyright information:</b></p><p>Taken from "Bunched, the homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth"</p><p>http://www.biomedcentral.com/1471-213X/8/10</p><p>BMC Developmental Biology 2008;8():10-10.</p><p>Published online 28 Jan 2008</p><p>PMCID:PMC2253523.</p><p></p>e () driver line. (A) EP-mediated expression of does not produce a wing bending phenotype. (B) Overexpression of in the dorsal wing compartment leads to wing bending (was co-expressed as a control). The bent-down wing phenotype is enhanced when the EP-insertion (C) or a transgene (D) is used to co-overexpress . Expression of from the EP consistently results in stronger phenotypes than from the transgene. (E) Co-overexpression of leads to a complete suppression of the bent-down wing phenotype. (F) Expression of suppresses the bent-down wing phenotype, and the suppression is even stronger when a copy of is removed (G), indicative of a dominant negative effect of on . Consistently, co-expression of interferes with the suppressing effect of (H)

Bunched, the homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth-0

<p><b>Copyright information:</b></p><p>Taken from "Bunched, the homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth"</p><p>http://www.biomedcentral.com/1471-213X/8/10</p><p>BMC Developmental Biology 2008;8():10-10.</p><p>Published online 28 Jan 2008</p><p>PMCID:PMC2253523.</p><p></p>results in a reduction of eye and head size (B) as compared to the control (A). This growth deficit is rescued by overexpression of a transgene (C). (D) Schematic representation of the six Bun protein isoforms. The putative Bun transcription factors have distinct N-termini but an identical C-terminal region (common region), including the TSC-box (DNA-binding) and an adjacent leucine zipper (homo- and heterodimerization) encoded by the very 3' exon (E). All Bun isoforms except for BunC also contain a conserved region N-terminally to the TSC-box that is present in all mammalian TSC-22/Dip/Bun family members. In addition, BunA and BunF possess two domains in their N-terminal regions that are conserved among mammalian homologs ([13], domain 1 aligns to BunA amino acids 369-82 [Swissprot:]). The eight EMS-induced mutations isolated in the eyFLP/FRT screen (indicated in red) affect only BunA and BunF. (E) The genomic region of according to FlyBase [39]. The six transcripts share the last exon but have distinct 5' exons. UTRs are shown in white and ORFs in black. P-element insertions used for the jump-out screens and deletions obtained in these screens are indicated. Arrowheads indicate the directions of transcription that can be driven by the respective EP insertions. The P-element and the deletions derived from it as well as the EMS-induced alleles affect both and but are referred to as alleles. Genotypes are: (A) , ; (B) , ; (C) , ;

Bunched, the homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth-5

<p><b>Copyright information:</b></p><p>Taken from "Bunched, the homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth"</p><p>http://www.biomedcentral.com/1471-213X/8/10</p><p>BMC Developmental Biology 2008;8():10-10.</p><p>Published online 28 Jan 2008</p><p>PMCID:PMC2253523.</p><p></p>results in a reduction of eye and head size (B) as compared to the control (A). This growth deficit is rescued by overexpression of a transgene (C). (D) Schematic representation of the six Bun protein isoforms. The putative Bun transcription factors have distinct N-termini but an identical C-terminal region (common region), including the TSC-box (DNA-binding) and an adjacent leucine zipper (homo- and heterodimerization) encoded by the very 3' exon (E). All Bun isoforms except for BunC also contain a conserved region N-terminally to the TSC-box that is present in all mammalian TSC-22/Dip/Bun family members. In addition, BunA and BunF possess two domains in their N-terminal regions that are conserved among mammalian homologs ([13], domain 1 aligns to BunA amino acids 369-82 [Swissprot:]). The eight EMS-induced mutations isolated in the eyFLP/FRT screen (indicated in red) affect only BunA and BunF. (E) The genomic region of according to FlyBase [39]. The six transcripts share the last exon but have distinct 5' exons. UTRs are shown in white and ORFs in black. P-element insertions used for the jump-out screens and deletions obtained in these screens are indicated. Arrowheads indicate the directions of transcription that can be driven by the respective EP insertions. The P-element and the deletions derived from it as well as the EMS-induced alleles affect both and but are referred to as alleles. Genotypes are: (A) , ; (B) , ; (C) , ;

Bunched, the homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth-1

<p><b>Copyright information:</b></p><p>Taken from "Bunched, the homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth"</p><p>http://www.biomedcentral.com/1471-213X/8/10</p><p>BMC Developmental Biology 2008;8():10-10.</p><p>Published online 28 Jan 2008</p><p>PMCID:PMC2253523.</p><p></p>are indicated. A precise excision of the P-element serves as control (A). Eyes largely homozygous for mutations (B and C) and for the deletion allele (F) are small. (A'-F') Tangential sections of mosaic eyes containing homozygous mutant photoreceptors (marked by the lack of pigmentation) surrounded by heterozygous (and therefore wild-type sized) photoreceptors. A cell size reduction is apparent in clones of mutant cells (B', C', and F'). (D') and (E') mutant photoreceptors do not differ from control photoreceptors. (H) Rhabdomere size is 40% decreased in mutant ommatidia (B', only clones without differentiation defects were analyzed). The area enclosed by the rhabdomeres of photoreceptors R1-6 in unpigmented mutant ommatidia relative to neighboring pigmented ommatidia was measured (= 7). Clones were induced early during development (24–48 h after egg deposition (AED)) using the hsFLP/FRT technique. (G) Statistical analysis of ommatidia number in mosaic eyes (= 6) relative to control lines (= 6, is used as control for EMS-induced alleles, and precise excisions of the respective P-element insertions for the deletion alleles). Mosaic eyes largely consisting of and mutant clones have a normal number of ommatidia. Eyes from female flies were examined in all analyses