Cryptocephal, the ATF4, Is a Specific Coactivator for Ecdysone Receptor Isoform B2

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The ecdysone receptor is a heterodimer of two nuclear receptors, the Ecdysone receptor (EcR) and Ultraspiracle (USP). In Drosophila melanogaster, three EcR isoforms share common DNA and ligand-binding domains, but these proteins differ in their most N-terminal regions and, consequently, in the activation domains (AF1s) contained therein. The transcriptional coactivators for these domains, which impart unique transcriptional regulatory properties to the EcR isoforms, are unknown. Activating transcription factor 4 (ATF4) is a basic-leucine zipper transcription factor that plays a central role in the stress response of mammals. Here we show that Cryptocephal (CRC), the Drosophila homolog of ATF4, is an ecdysone receptor coactivator that is specific for isoform B2. CRC interacts with EcR-B2 to promote ecdysone-dependent expression of ecdysis-triggering hormone (ETH), an essential regulator of insect molting behavior. We propose that this interaction explains some of the differences in transcriptional properties that are displayed by the EcR isoforms, and similar interactions may underlie the differential activities of other nuclear receptors with distinct AF1-coactivators.

Vyšlo v časopise: Cryptocephal, the ATF4, Is a Specific Coactivator for Ecdysone Receptor Isoform B2. PLoS Genet 8(8): e32767. doi:10.1371/journal.pgen.1002883
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002883

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Zdroje

1. WarnmarkA, TreuterE, WrightAP, GustafssonJA (2003) Activation functions 1 and 2 of nuclear receptors: molecular strategies for transcriptional activation. Mol Endocrinol 17 : 1901–1909.

2. CherbasL, HuX, ZhimulevI, BelyaevaE, CherbasP (2003) EcR isoforms in Drosophila: testing tissue-specific requirements by targeted blockade and rescue. Development 130 : 271–284.

3. Dela CruzFE, KirschDR, HeinrichJN (2000) Transcriptional activity of Drosophila melanogaster ecdysone receptor isoforms and ultraspiracle in Saccharomyces cerevisiae. J Mol Endocrinol 24 : 183–191.

4. HuX, CherbasL, CherbasP (2003) Transcription activation by the ecdysone receptor (EcR/USP): identification of activation functions. Mol Endocrinol 17 : 716–731.

5. MouilletJF, HenrichVC, LezziM, VogtliM (2001) Differential control of gene activity by isoforms A, B1 and B2 of the Drosophila ecdysone receptor. Eur J Biochem 268 : 1811–1819.

6. TalbotWS, SwyrydEA, HognessDS (1993) Drosophila tissues with different metamorphic responses to ecdysone express different ecdysone receptor isoforms. Cell 73 : 1323–1337.

7. GatesJ, LamG, OrtizJA, LossonR, ThummelCS (2004) rigor mortis encodes a novel nuclear receptor interacting protein required for ecdysone signaling during Drosophila larval development. Development 131 : 25–36.

8. BaiJ, UeharaY, MontellDJ (2000) Regulation of invasive cell behavior by taiman, a Drosophila protein related to AIB1, a steroid receptor coactivator amplified in breast cancer. Cell 103 : 1047–1058.

9. SedkovY, ChoE, PetrukS, CherbasL, SmithST, et al. (2003) Methylation at lysine 4 of histone H3 in ecdysone-dependent development of Drosophila. Nature 426 : 78–83.

10. BadenhorstP, XiaoH, CherbasL, KwonSY, VoasM, et al. (2005) The Drosophila nucleosome remodeling factor NURF is required for Ecdysteroid signaling and metamorphosis. Genes Dev 19 : 2540–2545.

11. ZhuJ, ChenL, SunG, RaikhelAS (2006) The competence factor betaFtz-F1 potentiates ecdysone receptor activity via recruiting a p160/SRC coactivator. Mol Cell Biol 26 : 9402–9412.

12. BecksteadR, OrtizJA, SanchezC, ProkopenkoSN, ChambonP, et al. (2001) Bonus, a Drosophila homolog of TIF1 proteins, interacts with nuclear receptors and can inhibit betaFTZ-F1-dependent transcription. Mol Cell 7 : 753–765.

13. TsaiCC, KaoHY, YaoTP, McKeownM, EvansRM (1999) SMRTER, a Drosophila nuclear receptor coregulator, reveals that EcR-mediated repression is critical for development. Mol Cell 4 : 175–186.

14. ParkY, FilippovV, GillSS, AdamsME (2002) Deletion of the ecdysis-triggering hormone gene leads to lethal ecdysis deficiency. Development 129 : 493–503.

15. HewesRS, SchaeferAM, TaghertPH (2000) The cryptocephal gene (ATF4) encodes multiple basic-leucine zipper proteins controlling molting and metamorphosis in Drosophila. Genetics 155 : 1711–1723.

16. FasslerJ, LandsmanD, AcharyaA, MollJR, BonovichM, et al. (2002) B-ZIP proteins encoded by the Drosophila genome: evaluation of potential dimerization partners. Genome Res 12 : 1190–1200.

17. HadornE, GloorH (1943) Cryptocephal ein spat wirkender Letalfaktor bei Drosophila melanogaster. Revue suisse Zool 50 : 256–261.

18. BrownHL, CherbasL, CherbasP, TrumanJW (2006) Use of time-lapse imaging and dominant negative receptors to dissect the steroid receptor control of neuronal remodeling in Drosophila. Development 133 : 275–285.

19. GauthierSA, HewesRS (2006) Transcriptional regulation of neuropeptide and peptide hormone expression by the Drosophila dimmed and cryptocephal genes. J Exp Biol 209 : 1803–1815.

20. OsterwalderT, YoonKS, WhiteBH, KeshishianH (2001) A conditional tissue-specific transgene expression system using inducible GAL4. PNAS 98 : 12596–12601.

21. ParkY, ZitnanD, GillSS, AdamsME (1999) Molecular cloning and biological activity of ecdysis-triggering hormones in Drosophila melanogaster. FEBS Lett 463 : 133–138.

22. ZitnanD, RossLS, ZitnanovaI, HermesmanJL, GillSS, et al. (1999) Steroid induction of a peptide hormone gene leads to orchestration of a defined behavioral sequence. Neuron 23 : 523–535.

23. Riddiford LM (1993) Hormones and Drosophila development. In: The development of Drosophila melanogaster. Bate M, Martinez Arias A, editors. Cold Spring Harbor: Cold Spring Harbor Laboratory Press. 899–939.

24. KinganTG, AdamsME (2000) Ecdysteroids regulate secretory competence in Inka cells. J Exp Biol 203 : 3011–3018.

25. MillerM (2009) The importance of being flexible: the case of basic region leucine zipper transcriptional regulators. Curr Protein Pept Sci 10 : 244–269.

26. VinsonC, AcharyaA, TaparowskyEJ (2006) Deciphering B-ZIP transcription factor interactions in vitro and in vivo. Biochim Biophys Acta 1759 : 4–12.

27. BorukM, SavoryJG, HacheRJ (1998) AF-2-dependent potentiation of CCAAT enhancer binding protein beta-mediated transcriptional activation by glucocorticoid receptor. Mol Endocrinol 12 : 1749–1763.

28. TeyssierC, BelguiseK, GaltierF, ChalbosD (2001) Characterization of the physical interaction between estrogen receptor alpha and JUN proteins. J Biol Chem 276 : 36361–36369.

29. WardellSE, BoonyaratanakornkitV, AdelmanJS, AronheimA, EdwardsDP (2002) Jun dimerization protein 2 functions as a progesterone receptor N-terminal domain coactivator. Mol Cell Biol 22 : 5451–5466.

30. RutkowskiDT, KaufmanRJ (2003) All roads lead to ATF4. Dev Cell 4 : 442–444.

31. KohlerJJ, MetalloSJ, SchneiderTL, SchepartzA (1999) DNA specificity enhanced by sequential binding of protein monomers. Proc Natl Acad Sci U S A 96 : 11735–11739.

32. EmeryIF, BedianV, GuildGM (1994) Differential expression of Broad-Complex transcription factors may forecast tissue-specific developmental fates during Drosophila metamorphosis. Development 120 : 3275–3287.

33. BainbridgeSP, BownesM (1981) Staging the metamorphosis of Drosophila melanogaster. J Embryol Exp Morphol 66 : 57–80.

34. McGuireSE, MaoZ, DavisRL (2004) Spatiotemporal gene expression targeting with the TARGET and gene-switch systems in Drosophila. Sci STKE 2004: pl6.

35. DietzlG, ChenD, SchnorrerF, SuKC, BarinovaY, et al. (2007) A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature 448 : 151–156.

36. ColombaniJ, BianchiniL, LayalleS, PondevilleE, Dauphin-VillemantC, et al. (2005) Antagonistic actions of ecdysone and insulins determine final size in Drosophila. Science 310 : 667–670.

37. HewesRS, ParkD, GauthierSA, SchaeferAM, TaghertPH (2003) The bHLH protein Dimmed controls neuroendocrine cell differentiation in Drosophila. Development 130 : 1771–1781.