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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Down-Regulation


Psychiatry related information on Down-Regulation


High impact information on Down-Regulation


Chemical compound and disease context of Down-Regulation


Biological context of Down-Regulation

  • Phosphorylation and downregulation of Yan is facilitated by a protein called Mae [21].
  • Therefore, Drosophila cyclin E, which forms a complex with the Dmcdc2c kinase, controls progression through S phase and its down-regulation limits embryonic proliferation [22].
  • We propose that ESCRT-I represents a conserved component of the endosomal sorting machinery that functions in both yeast and mammalian cells to couple ubiquitin modification to protein sorting and receptor downregulation in the MVB pathway [23].
  • The downregulation of PS1 in these U937 transfectants results in reduced growth with an increased fraction of the cells in apoptosis [24].
  • Whereas the down-regulation of myc seems to be an early event of F9 differentiation occurring within the first 24 h, the post-transcriptional regulation of p53 occurs at a later stage (two to three days), possibly as a consequence of cell cycle changes [25].

Anatomical context of Down-Regulation


Associations of Down-Regulation with chemical compounds

  • We have located the distal boundary of the tyrosine kinase domain of the EGF receptor and have identified a distinct sequence in the C' terminus required for EGF-dependent receptor internalization, leading to receptor down-regulation and degradation [31].
  • Conversely, down-regulation of NCX by siRNA compromised neuronal Ca2+ handling, transforming the Ca2+ transient elicited by non-excitotoxic glutamate concentrations into a lethal Ca2+overload [32].
  • Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells [33].
  • Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage [34].
  • A mutant form of the SIVmac239 Nef, which contains changes in a putative SH3-binding domain (amino acids 104 and 107 have been changed from PxxP to AxxA), does not associate with cellular serine/threonine kinases, but is fully active in CD4 downregulation and associates with the cellular tyrosine kinase Src [35].

Gene context of Down-Regulation


Analytical, diagnostic and therapeutic context of Down-Regulation


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  19. Regional myocardial downregulation of the inhibitory guanosine triphosphate-binding protein (Gi alpha 2) and beta-adrenergic receptors in a porcine model of chronic episodic myocardial ischemia. Hammond, H.K., Roth, D.A., McKirnan, M.D., Ping, P. J. Clin. Invest. (1993) [Pubmed]
  20. Acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor-induced lethal hepatitis. Marí, M., Colell, A., Morales, A., Pañeda, C., Varela-Nieto, I., García-Ruiz, C., Fernández-Checa, J.C. J. Clin. Invest. (2004) [Pubmed]
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  22. Cyclin E controls S phase progression and its down-regulation during Drosophila embryogenesis is required for the arrest of cell proliferation. Knoblich, J.A., Sauer, K., Jones, L., Richardson, H., Saint, R., Lehner, C.F. Cell (1994) [Pubmed]
  23. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Katzmann, D.J., Babst, M., Emr, S.D. Cell (2001) [Pubmed]
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  33. Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells. Bories, D., Raynal, M.C., Solomon, D.H., Darzynkiewicz, Z., Cayre, Y.E. Cell (1989) [Pubmed]
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