The CPT1C 5′UTR contains a repressing upstream open reading frame that is regulated by cellular energy availability and AMPK

PLoS ONE

Volumn 6, Issue 9, 2011, Pages

  Lohse, Ines ^a   Reilly, Patrick ^a,b   Zaugg, Kathrin ^a  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^b DIVISION OF MEDICAL ONCOLOGY   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

ACYLTRANSFERASE; BOVINE SERUM ALBUMIN; CARNITINE PALMITOYLTRANSFERASE IC; COMPOUND C; GLUCOSE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; LUCIFERASE; MESSENGER RNA; METFORMIN; PALMITIC ACID; PROTEIN SERINE THREONINE KINASE INHIBITOR; UNCLASSIFIED DRUG; (6 (4 (2 PIPERIDIN 1 YLETHOXY)PHENYL)) 3 PYRIDIN 4 YLPYRAZOLO(1,5 A)PYRIMIDINE; (6-(4-(2-PIPERIDIN-1-YLETHOXY)PHENYL))-3-PYRIDIN-4-YLPYRAZOLO(1,5-A)PYRIMIDINE; CARNITINE PALMITOYLTRANSFERASE; PALMITIC ACID DERIVATIVE; PYRAZOLE DERIVATIVE; PYRIMIDINE DERIVATIVE;

5' UNTRANSLATED REGION; ARTICLE; CELL ENERGY; CONTROLLED STUDY; DRUG EFFECT; ENERGY METABOLISM; ENZYME INHIBITION; FETUS; GENE REPRESSION; HUMAN; HUMAN CELL; NUCLEOTIDE SEQUENCE; OPEN READING FRAME; RNA SEQUENCE; TRANSLATION REGULATION; CELL HYPOXIA; CHEMISTRY; DRUG ANTAGONISM; GENETICS; METABOLISM; MUTATION; PHYSIOLOGY; PROTEIN SYNTHESIS; RNA INTERFERENCE; TIME; TUMOR CELL LINE; WESTERN BLOTTING;

5' UNTRANSLATED REGIONS; AMP-ACTIVATED PROTEIN KINASES; BLOTTING, WESTERN; CARNITINE O-PALMITOYLTRANSFERASE; CELL HYPOXIA; CELL LINE, TUMOR; ENERGY METABOLISM; GLUCOSE; HUMANS; LUCIFERASES; MUTATION; OPEN READING FRAMES; PALMITATES; PROTEIN BIOSYNTHESIS; PYRAZOLES; PYRIMIDINES; RNA INTERFERENCE; RNA, MESSENGER; SERUM ALBUMIN, BOVINE; TIME FACTORS;

EID: 80053056984     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0021486     Document Type: Article

References (44)

1. Kozak M, (1991) Structural features in eukaryotic mRNAs that modulate the initiation of translation. J Biol Chem 266: 19867-19870.
2. Morris DR, Geballe AP, (2000) Upstream open reading frames as regulators of mRNA translation. Mol Cell Biol 20: 8635-8642.
3. Calvo SE, Pagliarini DJ, Mootha VK, (2009) Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans. PNAS 106: 7507-7512.
4. Spevak CC, Park E-H, Geballe AP, Pelletier J, Sachs MS, (2006) her-2 upstream open reading frame effects on the use of downstream initiation codons. Biochemical and Biophysical Research Communications 350: 834-841.
5. Schlüter G, Boinska D, Nieman-Seyde S-C, (2000) Evidence for Translational Repression of the SOCS-1 Major Open Reading Frame by an Upstream Open Reading Frame. Biochemical and Biophysical Research Communications 268: 255-261.
6. Vilela C, McCarthy JE, (2003) Regulation of fungal gene expression via short open reading frames in the mRNA 5′untranslated region. Mol Microbiol 49: 859-867.
7. Rahmani F, Hummel M, Schuurmans J, Wiese-Klinkenberg A, Smeekens S, et al. (2009) Succrose control of translation mediated by an upstream open reading frame-encoded peptide. Plant Physiology 150: 1356-1367.
8. Mühlemann O, Eberle AB, Stalder L, Zamudio-Orozco R, (2008) Recognition and elemination of nonsense mRNA. Biochimica et Biophysica Acta 1779: 538-549.
9. Wiestner A, Schlemper RJ, van der Maas AP, Skoda RC, (1998) An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia. Nat Genet 18: 49-52.
10. Liu L, Dilworth D, Gao L, Monzon J, Summers A, et al. (1999) Mutation of the CDKN2A 5′ UTR creates an aberrant initiation codon and predisposes to melanoma. Nat Genet 21: 128-132.
11. Wen Y, Liu Y, Xu Y, Zhao Y, Hua R, et al. (2009) Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis. Nat Genet 41: 228-233.
12. Price N, van der Leij F, Jackson V, (2002) A novel brain-expressed protein related to carnitine palmitoyltransferase I. Genomics 80: 433-442.
13. Jogl G, Tong L, (2003) Crystal structure of carnitine acetyltransferase and implications for the catalytic mechanism and fatty acid transport. Cell 112: 113-122.
14. Bonnefont JP, Djouadi F, Prip-Buus C, Gobin S, Munnich A, et al. (2004) Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects. Mol Aspects Med 25: 495-520.
15. Wolfgang MJ, Kurama T, Dai Y, (2006) The brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis. Proc Natl Acad Sci U S A 103: 7282-7287.
16. Wolfgang MJ, Cha SH, Millington DS, (2008) Brain-specific carnitine palmitoyl-transferase-1c: role in CNS fatty acid metabolism, food intake, and body weight. J Neurochem 105: 1550-1559.
17. Gao XF, Chen W, Kong XP, Xu AM, Wang ZG, et al. (2009) Enhanced susceptibility of Cpt1c knockout mice to glucose intolerance induced by a hight-fat diet involves elevated hepatic gluconeogenesis and decreased skeletal muscle glucose uptake. Diabetologia 52 (5): 912-20.
18. Dai Y, Wolfgang MJ, Cha SH, Lane MD, (2007) Localization and effect of ectopic expression of CPT1c in CNS feeding centers. Biochem Biophys Res Commun 359: 469-474.
19. Sierra AY, Gratacos E, Carrasco P, (2008) CPT1c is localized in endoplasmic reticulum of neurons and has carnitine palmitoyltransferase activity. J Biol Chem 283: 6878-6885.
20. Mayer CM, Belsham DD, (2010) Palmitate attenuates insulin signaling and induces endoplasmic reticulum stress and apoptosis in hypothalamic neurons: rescue of resistance and apoptosis through adenosine 5′ monophosphate-activated protein kinase activation. Endocrinology 151 (2): 576-85.
21. de Pablo MA, Susin SA, Jacotot E, Larochette N, Costantini P, et al. (1999) Palmitate induces apoptosis via a direct effect on mitochondria. Apoptosis 4: 81-87.
22. Jump DB, Clarke SD, (1999) Regulation of Gene Expression by Dietary Fat. Annu Rev Nutr 19: 63-90.
23. Obici S, Feng Z, Arduini A, Conti R, Rossetti L, (2003) Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production. Nat Med 9: 756-761.
24. Lavrentyev EN, Matta SG, Cook GA, (2004) Expression of three carnitine palmitoyltransferase-I isoforms in 10 regions of the rat brain during feeding, fasting, and diabetes. Biochem Biophys Res Commun 315: 174-178.
25. Minokoshi Y, Shiuchi T, Lee S, Suzuki A, Okamoto S, (2008) Role of hypothalamic AMP-kinase in food intake regulation. Nutrition 24 (9): 786-90.
26. Canto C, Auwerx J, (2010) AMP-activated protein kinase and its downstream transcriptional pathways. Cell Mol Life Sci (2010) 67: 3407-3423.
27. Scharrer E, (1999) Control of Food Intake by Fatty Acid Oxidation and Ketogenesis. Nutrition 15: 704-714.
28. Wolfgang MJ, Lane MD, (2006a) The role of hypothalamic malonyl-CoA in energy homeostasis. J Biol Chem 281: 37265-37269.
29. Shimokawa T, Kumar MV, Lane MD, (2002) Effect of a fatty acid synthase inhibitor on food intake and expression of hypothalamic neuropeptides. Proc Natl Acad Sci USA 99: 66-71.
30. Migrenne S, Magnan C, Cruciani-Guglielmacci C, (2007) Fatty acid sensing and nervous control of Energy homeostasis. Diabetis & Metabolism 33: 177-182.
31. Benoit SC, Kemp CJ, Elias CF, Abplanalp W, Herman JP, et al. (2009) Palmitic acid mediates hypothalamic insulin resistance by altering PKC-theta subcellular localization in rodents. J Clin Invest 119: 2577-2589.
32. Hu Z, Cha SH, Chohnan S, Lane MD, (2003) Hypothalamic malonyl-CoA as a mediator of feeding behaviour. Proc Natl Acad Sci USA 100: 12624-12629.
33. Hardie DG, (2004) AMP-activated protein kinase: a master switch in glucose and lipid metabolism. Rev Endocr Metab Disord 5: 119-125.
34. Wolfgang MJ, Lane MD, (2006b) Control of energy homeostasis: role of enzymes and intermediates of fatty acid metabolism in the central nervous system. Annu Rev Nutr 26: 23-44.
35. Chan AY, Dyck JR, (2005) Activation of AMP-activated protein kinase (AMPK) inhibits protein synthesis: a potential strategy to prevent the development of cardiac hypertrophy. Can J Physiol Pharmacol 83: 24-28.
36. Chau-Van C, Gamba M, Salvi R, Gaillard RC, Pralong FP, (2006) Metformin Inhibits Adenosine 5′-Monophosphate-Activated Kinase Activation and Prevents Increases in Neuropeptide Y Expression in Cultured Hypothalamic Neurons. Endocrinology 148 (2): 507-511.
37. Lim CT, Kola B, Korbonits M, (2010) AMPK as a mediator of hormonal signalling. Journal of Molecular Endocrinology 44: 87-97.
38. Fediuc S, Gaidhu MP, Ceddia RB, (2006) Regulation of AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation by palmitate in skeletal muscle cells. The Journal of Lipid Research 47: 412-420.
39. Karagounis LG, Hawley JA, (2009) The 5′ adenosine monophosphate-activated protein kinase: Regulating the ebb and flow of cellular energetics. Int J Biochem Cell Biol 41 (12): 2360-3.
40. Yang CS, Lam CK, Chari M, Cheung G, Kokorovic A, et al. (2010) Hypothalamic AMPK Regulates Glucose Production. Diabetis doi:10.2337/db10-0221.
41. He W, Lam TK, Obici S, Rossetti L, (2006) Molecular disruption of hypothalamic nutrient sensing induces obesity. Nat Neurosci 9: 227-233.
42. Ramamurthy S, Ronnett GV, (2006) Developing a head for energy sensing: AMP-activated protein kinase as a multifunctional metabolic sensor in the brain. J Physiol 574 (Pt 1): 85-93.
43. Sangiao-Alvarellos S, Varela L, Vazquez MJ, Da Boit K, Saha AK, et al. (2010) Influence of ghrelin and GH deficiency on AMPK and hypothalamic lipid metabolism. Journal of Neuroendocrinology 22: 543-556.
44. McGarry JD, Mills SE, Long CS, Foster DW, (1983) Observations on the affinity for carnitine, and malonyl-CoA sensitivity, of carnitine palmitoyltransferase I in animal and human tissues. Demonstration of the presence of malonyl-CoA in non-hepatic tissues of the rat. Biochem J 214: 21-28.