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. 2000 Jul 15;349(Pt 2):629–634. doi: 10.1042/0264-6021:3490629

Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologues.

T Furuyama 1, T Nakazawa 1, I Nakano 1, N Mori 1
PMCID: PMC1221187  PMID: 10880363

Abstract

daf-16 is a forkhead-type transcription factor, functioning downstream of insulin-like signals, and is known to be critical to the regulation of life span in Caenorhabditis elegans. Mammalian DAF-16 homologues include AFX, FKHR and FKHRL1, which contain a conserved forkhead domain and three putative phosphorylation sites for the Ser/Thr kinase Akt/protein kinase B (PKB), as well as for DAF-16. To assess the function of the homologues, we examined tissue distribution patterns of mRNAs for DAF-16 homologues in mice. In the embryos, expressions of AFX, FKHR and FKHRL1 mRNAs were complementary to each other and were highest in muscle, adipose tissue and embryonic liver. The characteristic expression pattern remained in the adult, except that signals of FKHRL1 became evident in more tissues, including the brain. In order to clarify whether each DAF-16 homologue had different target genes, we determined the consensus sequences for the binding of DAF-16 and the mouse homologues. The binding sequences for all four proteins shared a core sequence, TTGTTTAC, daf-16 family protein-binding element (DBE) binding protein. However, electrophoretic mobility shift assay showed that the binding affinity of DAF-16 homologues to the core sequence was stronger than that to the insulin-responsive element in the insulin-like growth factor binding protein-1 promoter region, which has been identified as a binding sequence for them. We identified one copy of the DBE upstream of the first exon of sod-3 by searching the genomic database of C. elegans. Taken together, DAF-16 homologues can fundamentally regulate the common target genes in insulin-responsive tissues and the specificity to target genes of each protein is partially determined by the differences in their expression patterns.

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Selected References

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  1. Altomare D. A., Lyons G. E., Mitsuuchi Y., Cheng J. Q., Testa J. R. Akt2 mRNA is highly expressed in embryonic brown fat and the AKT2 kinase is activated by insulin. Oncogene. 1998 May 7;16(18):2407–2411. doi: 10.1038/sj.onc.1201750. [DOI] [PubMed] [Google Scholar]
  2. Anderson M. J., Viars C. S., Czekay S., Cavenee W. K., Arden K. C. Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily. Genomics. 1998 Jan 15;47(2):187–199. doi: 10.1006/geno.1997.5122. [DOI] [PubMed] [Google Scholar]
  3. Apfeld J., Kenyon C. Cell nonautonomy of C. elegans daf-2 function in the regulation of diapause and life span. Cell. 1998 Oct 16;95(2):199–210. doi: 10.1016/s0092-8674(00)81751-1. [DOI] [PubMed] [Google Scholar]
  4. Biggs W. H., 3rd, Meisenhelder J., Hunter T., Cavenee W. K., Arden K. C. Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7421–7426. doi: 10.1073/pnas.96.13.7421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Borkhardt A., Repp R., Haas O. A., Leis T., Harbott J., Kreuder J., Hammermann J., Henn T., Lampert F. Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23). Oncogene. 1997 Jan 16;14(2):195–202. doi: 10.1038/sj.onc.1200814. [DOI] [PubMed] [Google Scholar]
  6. Brunet A., Bonni A., Zigmond M. J., Lin M. Z., Juo P., Hu L. S., Anderson M. J., Arden K. C., Blenis J., Greenberg M. E. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999 Mar 19;96(6):857–868. doi: 10.1016/s0092-8674(00)80595-4. [DOI] [PubMed] [Google Scholar]
  7. Friedman D. B., Johnson T. E. A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics. 1988 Jan;118(1):75–86. doi: 10.1093/genetics/118.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Galili N., Davis R. J., Fredericks W. J., Mukhopadhyay S., Rauscher F. J., 3rd, Emanuel B. S., Rovera G., Barr F. G. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993 Nov;5(3):230–235. doi: 10.1038/ng1193-230. [DOI] [PubMed] [Google Scholar]
  9. Guo S., Rena G., Cichy S., He X., Cohen P., Unterman T. Phosphorylation of serine 256 by protein kinase B disrupts transactivation by FKHR and mediates effects of insulin on insulin-like growth factor-binding protein-1 promoter activity through a conserved insulin response sequence. J Biol Chem. 1999 Jun 11;274(24):17184–17192. doi: 10.1074/jbc.274.24.17184. [DOI] [PubMed] [Google Scholar]
  10. Honda Y., Honda S. The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J. 1999 Aug;13(11):1385–1393. [PubMed] [Google Scholar]
  11. Jazwinski S. M. Longevity, genes, and aging. Science. 1996 Jul 5;273(5271):54–59. doi: 10.1126/science.273.5271.54. [DOI] [PubMed] [Google Scholar]
  12. Kenyon C., Chang J., Gensch E., Rudner A., Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature. 1993 Dec 2;366(6454):461–464. doi: 10.1038/366461a0. [DOI] [PubMed] [Google Scholar]
  13. Kimura K. D., Tissenbaum H. A., Liu Y., Ruvkun G. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science. 1997 Aug 15;277(5328):942–946. doi: 10.1126/science.277.5328.942. [DOI] [PubMed] [Google Scholar]
  14. Kops G. J., de Ruiter N. D., De Vries-Smits A. M., Powell D. R., Bos J. L., Burgering B. M. Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature. 1999 Apr 15;398(6728):630–634. doi: 10.1038/19328. [DOI] [PubMed] [Google Scholar]
  15. Lin K., Dorman J. B., Rodan A., Kenyon C. daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science. 1997 Nov 14;278(5341):1319–1322. doi: 10.1126/science.278.5341.1319. [DOI] [PubMed] [Google Scholar]
  16. Morris J. Z., Tissenbaum H. A., Ruvkun G. A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature. 1996 Aug 8;382(6591):536–539. doi: 10.1038/382536a0. [DOI] [PubMed] [Google Scholar]
  17. Nakae J., Park B. C., Accili D. Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through a Wortmannin-sensitive pathway. J Biol Chem. 1999 Jun 4;274(23):15982–15985. doi: 10.1074/jbc.274.23.15982. [DOI] [PubMed] [Google Scholar]
  18. Nishihara E., Furuyama T., Yamashita S., Mori N. Expression of copper trafficking genes in the mouse brain. Neuroreport. 1998 Oct 5;9(14):3259–3263. doi: 10.1097/00001756-199810050-00023. [DOI] [PubMed] [Google Scholar]
  19. O'Brien R. M., Granner D. K. Regulation of gene expression by insulin. Physiol Rev. 1996 Oct;76(4):1109–1161. doi: 10.1152/physrev.1996.76.4.1109. [DOI] [PubMed] [Google Scholar]
  20. Ogg S., Paradis S., Gottlieb S., Patterson G. I., Lee L., Tissenbaum H. A., Ruvkun G. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature. 1997 Oct 30;389(6654):994–999. doi: 10.1038/40194. [DOI] [PubMed] [Google Scholar]
  21. Pierrou S., Hellqvist M., Samuelsson L., Enerbäck S., Carlsson P. Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending. EMBO J. 1994 Oct 17;13(20):5002–5012. doi: 10.1002/j.1460-2075.1994.tb06827.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rena G., Guo S., Cichy S. C., Unterman T. G., Cohen P. Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. J Biol Chem. 1999 Jun 11;274(24):17179–17183. doi: 10.1074/jbc.274.24.17179. [DOI] [PubMed] [Google Scholar]
  23. Tang E. D., Nuñez G., Barr F. G., Guan K. L. Negative regulation of the forkhead transcription factor FKHR by Akt. J Biol Chem. 1999 Jun 11;274(24):16741–16746. doi: 10.1074/jbc.274.24.16741. [DOI] [PubMed] [Google Scholar]

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