Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Notch signalling controls growth, differentiation and patterning during normal animal development; in humans, aberrant Notch signalling has been implicated in cancer and stroke. The mechanism of Notch signalling is thought to require cleavage of the receptor in response to ligand binding, movement of the receptor's intracellular domain to the nucleus, and binding of that intracellular domain to a CSL (for CBF1, Suppressor of Hairless, LAG-1) protein. Here we identify LAG-3, a glutamine-rich protein that forms a ternary complex together with the LAG-1 DNA-binding protein and the receptor's intracellular domain. Receptors with mutant ankyrin repeats that abrogate signal transduction are incapable of complex formation both in yeast and in vitro. Using RNA interference, we find that LAG-3 activity is crucial in Caenorhabditis elegans for both GLP-1 and LIN-12 signalling. LAG-3 is a potent transcriptional activator in yeast, and a Myc-tagged LAG-3 is predominantly nuclear in C. elegans. We propose that GLP-1 and LIN-12 promote signalling by recruiting LAG-3 to target promoters, where it functions as a transcriptional activator.
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PMID:LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway. 1083 Sep 67

During Caenorhabditis elegans gonadal development, a stochastic interaction between the LIN-12/Notch receptor and the LAG-2/Delta ligand initiates cell fate specification of two equivalent pre-anchor cell (AC)/pre-ventral uterine (VU) precursor cells. Both cells express lin-12 and lag-2 before specification, and a small difference in LIN-12 activity leads to the exclusive expression of lin-12 in VUs and lag-2 in the AC through an unknown feedback mechanism. In this Notch signaling process, the cleaved LIN-12/Notch intracellular domain (NICD) binds to the LAG-1/CSL transcriptional repressor, forming a transcriptional activator complex containing LAG-1 and NICD. Here we show that clustered LAG-1 binding sites in lin-12 and lag-1 are involved in regulating lin-12 and lag-1 expression during AC/VU cell fate specification. Both genes are expressed in VU cells, but not the AC, after specification. We also show that lin-12 is necessary for lag-1 expression in VU cells. Interestingly, lin-12 (null) animals express lag-1 in the AC, suggesting that LIN-12 signaling is necessary for the suppression of lag-1 expression in the AC. Ectopic expression of lag-1 cDNA in the AC causes a defect in the vulvaluterine (V-U) connection; therefore, LAG-1 should be eliminated in the AC to form a normal V-U connection at a later developmental stage in wild-type animals.
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PMID:LIN-12/Notch regulates lag-1 and lin-12 expression during anchor cell/ventral uterine precursor cell fate specification. 2348 78