Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Notch signalling pathway regulates cell-cell communication in higher eukaryotes. Cellular differentiation and tissue development relies on correct intercellular communication, accounting for the high interest in the Notch signalling pathway. Together with mastermind and CSL (CBF-1, Suppressor of Hairless, lag-2) DNA-binding proteins, Notch forms a complex that mediates transcriptional activation of the respective target genes. This activation is strictly controlled, and deregulation causes extreme developmental defects. In Drosophila, the stringency of the control system is given by the general Notch-antagonist Hairless. Hairless assembles in a repressor complex on Notch target genes, which involves Suppressor of Hairless and two corepressors, Groucho and C-terminal binding protein. In mammals, CBF-1 recruits corepressors on its own. In addition Hairless recruits also other proteins. One example is the Pros26.4 AAA-ATPase which specifically destabilises Hairless resulting in a novel positive regulation of Notch signalling. By inhibition of Notch, Hairless not only regulates cellular differentiation but also has anti-apoptotic functions. Moreover, many genetic interactions imply a cross-talk between Hairless and the EGF-receptor pathway, which might act independently of Notch. Surprisingly, no Hairless homologue has been identified in mammals so far, despite the high degree of conservation of other components of the pathway. This discrepancy might be resolved in the future, once all components of the repressor-complex in the different species have been identified. In conclusion, Hairless is a central component of the regulation of the Notch signalling pathway in Drosophila, and is hence essential for cell differentiation and tissue development in the fly.
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PMID:Hairless: the ignored antagonist of the Notch signalling pathway. 1736 57

The cell-fate specification of the anchor cell (AC) and a ventral uterine precursor cell (VU) in Caenorhabditis elegans is initiated by a stochastic interaction between LIN-12/Notch receptor and LAG-2/Delta ligand in two neighboring Z1.ppp and Z4.aaa cells. Both cells express lin-12 and lag-2 before specification, and a small difference in LIN-12 activity leads to the exclusive expressions of lin-12 in VU and lag-2 in the AC, through a feedback mechanism of unknown nature. Here we show that the expression pattern of lag-1/CSL, a transcriptional repressor itself that turns into an activator upon binding of the intracellular domain of Notch, overlaps with that of lin-12. Site-directed mutagenesis of LAG-1 binding sites in lag-1 maintains its expression in the AC, and eliminates it in the VU. Thus, AC/VU cell-fate specification appears to involve direct regulation of lag-1 expression by the LAG-1 protein, activating its transcription in VU cells, but repressing it in the AC.
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PMID:Clustered LAG-1 binding sites in lag-1/CSL are involved in regulating lag-1 expression during lin-12/Notch-dependent cell-fate specification. 2361 64