SMAD5 signaling: more than meets the nuclei was written by Orlowski, John. And the article was included in Cell Research in 2017.Category: piperazines This article mentions the following:
SMADs are essential transcriptional effectors of transforming growth factor-β (TGFβ)/TGFβ-related signaling that underlies embryonic development and adult homeostasis. A recent study by Fang et al in Cell Research adds to this biol. complexity by demonstrating an atypical cytoplasmic role for SMAD5 in modulating the bioenergetic homeostasis (i.e., glycolysis and mitochondrial respiration) of cells in response to fluctuations in intracellular pH that is independent of receptor signaling. SMAD5 was found to promote not only mitochondrial respiration but also glycolysis in a manner that was influenced by cytoplasmic pH (pHc) and seemingly distinct from the mitochondrial actions of ‘inactive’ cytoplasmic SMAD2. Increases in pHc above 7.2 promoted rapid accumulation of SMAD5 within the cytoplasm, whereas decreases below pHc 7.2 favored its accrual in the nucleus. Further mechanistic studies revealed that pHc-sensing by SMAD5 was conferred by one basic (lysine residues) and two acidic (aspartate and glutamate residues) amino acid clusters in its N-terminal MH1 domain. The pH sensitivity of SMAD5 is intriguing in light of recent reports showing that increases in intracellular pH (pHi) are required for the efficient differentiation of embryonic and adult stem cells. To determine whether there was a functional connection between these seemingly disparate events, the authors performed an elaborate series of experiments that compared the transcriptome profiles of wild-type (WT), SMAD5 knockout (KO) and LDN-193189 (an inhibitor of BMP signaling)-treated human embryonic stem cells (hESCs). The analyses revealed that loss of SMAD5 resulted in the downregulation of a unique subset of genes involved in cellular ion and metabolic homeostasis that were distinct from those affected by blocking BMP signaling. While the mechanism by which cytoplasmic SMAD5 directly stimulates glycolysis is largely resolved, how it regulates mitochondrial morphol. and respiration is less certain. In the experiment, the researchers used many compounds, for example, 4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4Category: piperazines).
4-(6-(4-(Piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline (cas: 1062368-24-4) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Category: piperazines
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics