Abstract:
:Orexin A and Orexin B (also known as hypocretins) are neuropeptides that bind two related G-coupled protein receptors (OXR1 and OXR2) and thus induce wakefulness, food consumption, and locomotion. Conversely, deletion of the orexin gene in mice produces a condition similar to canine and human narcolepsy. Despite the central importance of the orexin system in regulating wakefulness and feeding behavior, little is known about the downstream signaling mechanisms that achieve these effects. In this study, genomics techniques are used to probe this question and reveal that orexin activates the hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor whose pathogenic role in stimulating angiogenesis in hypoxic tumors has been the focus of intense investigation. Orexin-stimulated HIF-1 activity is due to both increased HIF-1alpha gene transcription and a down-regulation of von Hippel-Lindau (VHL), the E3 ubiquitin ligase that mediates the turnover of HIF-1 via the ubiquitin-proteasome pathway. Orexin-mediated activation of HIF-1 results in increased glucose uptake and higher glycolytic activity, as expected from studies of hypoxic cells. However, orexin receptor-expressing cells somehow override the HIF-1-mediated preference for funneling pyruvate into anaerobic glycolysis and instead favor ATP production through the tricarboxylic acid cycle and oxidative phosphorylation. These findings implicate HIF-1 as an important transcription factor in the hormone-mediated regulation of hunger and wakefulness.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Sikder D,Kodadek Tdoi
10.1101/gad.1584307subject
Has Abstractpub_date
2007-11-15 00:00:00pages
2995-3005issue
22eissn
0890-9369issn
1549-5477pii
21/22/2995journal_volume
21pub_type
杂志文章abstract::To investigate functional differences between RNA polymerases IIA and IIO (Pol IIA and Pol IIO), with hypo- and hyperphosphorylated carboxy-terminal repeat domains (CTDs), respectively, we have visualized the in vivo distributions of the differentially phosphorylated forms of Pol II on Drosophila polytene chromosomes....
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.12a.2329
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.930601
更新日期:2001-10-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.15.1829
更新日期:1994-08-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.323105.118
更新日期:2019-04-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.823200
更新日期:2000-09-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.7.843
更新日期:1988-07-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.915901
更新日期:2001-09-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.604610
更新日期:2010-11-01 00:00:00
abstract::TFIID is a multisubunit protein containing the TATA box-binding polypeptide (TBP) and associated factors (TFIID-TAFs) required for activated transcription by RNA polymerase II. TBPs from different eukaryotes contain a highly conserved carboxy-terminal domain and very divergent amino-terminal domains. Earlier studies p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.2.180
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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更新日期:1996-04-01 00:00:00
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journal_title:Genes & development
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更新日期:2008-03-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2010-01-15 00:00:00
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journal_title:Genes & development
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abstract::Until recently it was believed that Xenopus oocytes respond to heat shock by synthesizing the 70-kD heat shock protein hsp70 and that, uniquely amongst animal cell types, this response is mediated entirely at the translational level. This view has now been challenged and we present data that reevaluate the involvement...
journal_title:Genes & development
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更新日期:1987-07-01 00:00:00
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journal_title:Genes & development
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更新日期:2008-05-01 00:00:00
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章,评审
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更新日期:2007-12-01 00:00:00
abstract::The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6...
journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2015-04-15 00:00:00