Regulation of ANKRD9 expression by lipid metabolic perturbations

  • Wang, Xiaofei (Department of Biological Sciences, Tennessee State University) ;
  • Newkirk, Robert F. (Department of Biological Sciences, Tennessee State University) ;
  • Carre, Wilfrid (Department of Animal and Food Sciences, University of Delaware) ;
  • Ghose, Purnima (Department of Biological Sciences, Tennessee State University) ;
  • Igobudia, Barry (Department of Biological Sciences, Tennessee State University) ;
  • Townsel, James G. (Department of Physiology, Meharry Medical College) ;
  • Cogburn, Larry A. (Department of Animal and Food Sciences, University of Delaware)
  • Published : 2009.09.30


Fatty acid oxidation (FAO) defects cause abnormal lipid accumulation in various tissues, which provides an opportunity to uncover novel genes that are involved in lipid metabolism. During a gene expression study in the riboflavin deficient induced FAO disorder in the chicken, we discovered the dramatic increase in mRNA levels of an uncharacterized gene, ANKRD9. No functions have been ascribed to ANKRD9 and its orthologs, although their sequences are well conserved among vertebrates. To provide insight into the function of ANKRD9, the expression of ANKRD9 mRNA in lipidperturbed paradigms was examined. The hepatic mRNA level of ANKRD9 was repressed by thyroid hormone ($T_3$) and fasting, elevated by re-feeding upon fasting. However, ANKRD9 mRNA level is reduced in response to apoptosis. Transient transfection assay with green fluorescent protein tagged- ANKRD9 showed that this protein is localized within the cytoplasm. These findings point to the possibility that ANKRD9 is involved in intracellular lipid accumulation.


  1. Moreno, M., Lombardi, A., Beneduce, L., Silvestri, E., Pinna, G., Goglia, F. and Lanni, A. (2002) Are the effects of T3 on resting metabolic rate in euthyroid rats entirely caused by T3 itself? Endocrinology. 143, 504-510
  2. Xu, H. E., Lambert, M. H., Montana, V. G., Parks, D. J., Blanchard, S. G., Brown, P. J., Sternbach, D. D., Lehmann, J. M., Wisely, G. B., Willson, T. M., Kliewer, S. A. and Milburn, M. V. (1999) Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol. Cell. 3, 397-403
  3. Zhang, X., He, X., Fu, X. Y. and Chang, Z. (2006) Varp is a Rab21 guanine nucleotide exchange factor and regulates endosome dynamics. J. Cell Sci. 119, 1053-1062
  4. Lishko, P. V., Procko, E., Jin, X., Phelps, C. B. and Gaudet, R. (2007) The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity. Neuron. 54, 905-918
  5. Adibhatla, R. M. and Hatcher, J. F. (2008) Phospholipase A(2), reactive oxygen species, and lipid peroxidation in CNS pathologies. BMB Rep. 41, 560-567
  6. Larsson, P. K., Claesson, H. E. and Kennedy, B. P. (1998) Multiple splice variants of the human calcium-independent phospholipase A2 and their effect on enzyme activity. J. Biol. Chem. 273, 207-214
  7. Rader, K., Orlando, R. A., Lou, X. and Farquhar, M. G. (2000) Characterization of ANKRA, a novel ankyrin repeat protein that interacts with the cytoplasmic domain of megalin. J. Am. Soc. Nephrol. 11, 2167-2178
  8. White, H. B., 3rd, Nuwaysir, E. F., Komara, S. P., Anderson, D. A., Chang, S. J., Sherwood, T. A., Alphin, R. L. and Saylor, W. W. (1992) Effect of riboflavin-binding protein deficiency on riboflavin metabolism in the laying hen. Arch. Biochem. Biophys. 295, 29-34
  9. Mukhopadhyay, D., Plateroti, M., Anant, S., Nassir, F., Samarut, J. and Davidson, N. O. (2003) Thyroid hormone regulates hepatic triglyceride mobilization and apolipoprotein B messenger ribonucleic Acid editing in a murine model of congenital hypothyroidism. Endocrinology. 144, 711-719
  10. Wang, X., Carre, W., Saxton, A. M. and Cogburn, L. A. (2007) Manipulation of thyroid status and/or GH injection alters hepatic gene expression in the juvenile chicken. Cytogenet. Genome Res. 117, 174-1884
  11. Abrams, V. A., Han, C. C. and White, H. B., 3rd (1995) Riboflavin-deficient chicken embryos: hypoglycemia without dicarboxylic aciduria. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 111, 233-241
  12. Weiss, R. E., Murata, Y., Cua, K., Hayashi, Y., Seo, H. and Refetoff, S. (1998) Thyroid hormone action on liver, heart, and energy expenditure in thyroid hormone receptor beta-deficient mice. Endocrinology. 139, 4945-4952
  13. Jin, Q. H., Zhao, B. and Zhang, X. J. (2004) Cytochrome c release and endoplasmic reticulum stress are involved in caspase-dependent apoptosis induced by G418. Cell. Mol. Life Sci. 61, 1816-1825
  14. Cogburn, L. A., Porter, T. E., Duclos, M. J., Simon, J., Burgess, S. C., Zhu, J. J., Cheng, H. H., Dodgson, J. B. and Burnside, J. (2007) Functional genomics of the chicken--a model organism. Poult. Sci. 86, 2059-2094
  15. Boatright, K. M. and Salvesen, G. S. (2003) Mechanisms of caspase activation. Curr. Opin. Cell Biol. 15, 725-731
  16. Zhang, A., Li, C. W., Tsai, S. C. and Chen, J. D. (2007) Subcellular localization of ankyrin repeats cofactor-1 regulates its corepressor activity. J. Cell Biochem. 101, 1301-1315
  17. Lee, C. M. and White, H. B., 3rd (1996) Riboflavin-binding protein induces early death of chicken embryos. J. Nutr. 126, 523-528
  18. Abasht, B., Pitel, F., Lagarrigue, S., Le Bihan-Duval, E., Le Roy, P., Demeure, O., Vignoles, F., Simon, J., Cogburn, L., Aggrey, S., Vignal, A. and Douaire, M. (2006) Fatness QTL on chicken chromosome 5 and interaction with sex. Genet. Sel. Evol. 38, 297-311
  19. Winstead, M. V., Balsinde, J. and Dennis, E. A. (2000) Calcium-independent phospholipase A2: structure and function. BBA Mol. Cell Biol. Lipids. 1488, 28-39
  20. Beccavin, C., Chevalier, B., Cogburn, L. A., Simon, J. and Duclos, M. J. (2001) Insulin-like growth factors and body growth in chickens divergently selected for high or low growth rate. J. Endocrinol. 168, 297-306
  21. Gross, D. N., Miyoshi, H., Hosaka, T., Zhang, H. H., Pino, E. C., Souza, S., Obin, M., Greenberg, A. S. and Pilch, P. F. (2006) Dynamics of lipid droplet-associated proteins during hormonally stimulated lipolysis in engineered adipocytes: stabilization and lipid droplet binding of adipocyte differentiation-related protein/adipophilin. Mol. Endocrinol. 20, 459-466
  22. White, H. B., 3rd (1996) Sudden death of chicken embryos with hereditary riboflavin deficiency. J. Nutr. 126, S1303-1307
  23. Nicolas, V., Le Van Kim, C., Gane, P., Birkenmeier, C., Cartron, J. P., Colin, Y. and Mouro-Chanteloup, I. (2003) Rh-RhAG/ankyrin-R, a new interaction site between the membrane bilayer and the red cell skeleton, is impaired by Rh(null)-associated mutation. J. Biol. Chem. 278, 25526-25533
  24. Sachdev, S., Hoffmann, A. and Hannink, M. (1998) Nuclear localization of IkappaB alpha is mediated by the second ankyrin repeat: the IkappaB alpha ankyrin repeats define a novel class of cis-acting nuclear import sequences. Mol. Cell. Biol. 18, 2524-2534
  25. MacLachlan, I., Nimpf, J., White, H. B., 3rd and Schneider, W. J. (1993) Riboflavinuria in the rd chicken. 5'-splice site mutation in the gene for riboflavin-binding protein. J. Biol. Chem. 268, 23222-23226
  26. Miller, M. K., Bang, M. L., Witt, C. C., Labeit, D., Trombitas, C., Watanabe, K., Granzier, H., McElhinny, A. S., Gregorio, C. C. and Labeit, S. (2003) The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules. J. Mol. Biol. 333, 951-964
  27. Mosavi, L. K., Cammett, T. J., Desrosiers, D. C. and Peng, Z.-y. (2004) The ankyrin repeat as molecular architecture for protein recognition. Protein Sci. 13, 1435-1448
  28. Mishra, R., Emancipator, S. N., Miller, C., Kern, T. and Simonson, M. S. (2004) Adipose differentiation-related protein and regulators of lipid homeostasis identified by gene expression profiling in the murine db/db diabetic kidney. Am. J. Physiol. Renal Physiol. 286, F913-921
  29. Davis, L. H., Otto, E. and Bennett, V. (1991) Specific 33-residue repeat(s) of erythrocyte ankyrin associate with the anion exchanger. J. Biol. Chem. 266, 11163-11169

Cited by

  1. Genome-wide RNAi ionomics screen reveals new genes and regulation of human trace element metabolism vol.5, 2014,
  2. Network analysis of transcriptional regulation in response to intramuscular interferon-β-1a multiple sclerosis treatment vol.12, pp.2, 2012,
  3. Transcriptional profiling of liver in riboflavin-deficient chicken embryos explains impaired lipid utilization, energy depletion, massive hemorrhaging, and delayed feathering vol.19, pp.1, 2018,