High impact information on brk

• Furthermore, we present genetic and biochemical evidence that the brk silencer serves as a direct target for a protein complex consisting of the Smad homologs Mad/Medea and the zinc finger protein Schnurri [1].
• We then dissect the brk regulatory region and identify two separable elements with opposite properties, a constitutive enhancer and a Dpp morphogen-regulated silencer [1].
• Throughout development, Dpp transduction causes the graded transcriptional downregulation of the brinker (brk) gene [1].
• However, here we demonstrate that Dpp can also control gene expression indirectly by downregulating the expression of the brinker gene, which encodes a putative transcription factor that functions to repress Dpp targets [2].
• We propose that slow-proliferating cells upregulate Brk levels owing to a disadvantage in competing for, or in transducing, the Dpp survival signal [3].

Biological context of brk

• Excess brk expression activates the c-Jun amino-terminal kinase pathway, which in turn triggers apoptosis in these cells [3].
• We find that during embryogenesis, brk expression is derepressed in shn mutants [4].
• Thus, brk inhibition by Shn results in the upregulation of Dpp-responsive genes [5].
• Furthermore, Brk was able to compete with Mad for occupancy of this binding site [6].
• Here we show that the Brk protein functions as a repressor by binding to Dpp response elements [6].

Anatomical context of brk

• Brk is expressed by most of the oocyte associated follicle cells, starting from stage 8 of oogenesis [7].
• Some of these thresholds depend on a putative repressor, Brinker, which is expressed in the neurogenic ectoderm in response to the maternal Dorsal gradient and Dpp signaling [8].
• The salivary gland placode in brinker mutants appears reduced along both the anterior-posterior and dorso-ventral axis [9].
• Brk also functions as a rapid downstream signaling intermediate following calcium-induced differentiation in keratinocytes [10].

Associations of brk with chemical compounds

• Several Brk family kinases have an inhibitory effect on Ras pathway signaling from receptor tyrosine kinases [10].

Physical interactions of brk

• Repression of dpp targets by binding of brinker to mad sites [6].
• Direct transcriptional control of the Dpp target omb by the DNA binding protein Brinker [11].
• An optimal Brinker binding site is contained within an 800-bp enhancer from the tolloid gene, which has been identified as a genetic target of the Brinker repressor [8].

Regulatory relationships of brk

• For target genes to be activated, Dpp signalling must suppress transcription of a repressor encoded by the brinker (brk) gene [12].
• Mosaic analysis indicates that brk-expressing cells produce a short-range signal that can induce vein formation in adjacent omb-expressing cells [13].
• Furthermore, Brinker blocks transcriptional activation by ubiquitous Wg signaling [14].

Other interactions of brk

• These results suggest that the Sog inhibitor and Brk repressor work in concert to establish sharp dorsolateral limits of gene expression [15].
• Using this omb wing enhancer, we show that Brk is a sequence-specific DNA binding protein [11].
• This suggests that Brinker may have a widespread function in antagonizing Wg signaling [14].
• Finally, brinker and tsh produce similar mutant phenotypes in the ventral epidermis, and double mutants mimic overactive Wg signaling in this tissue [14].
• Here, we show that Wg-mediated repression of Ubx B depends on Brinker, which binds to the WRS-R [14].

References