Reference Report

Reference
Citation	Perrin, L., Bloyer, S., Ferraz, C., Agrawal, N., Sinha, P., Dura, J.M. (2003). The leucine zipper motif of the Drosophila AF10 homologue can inhibit PRE-mediated repression: implications for leukemogenic activity of human MLL-AF10 fusions. Mol. Cell. Biol. 23(1): 119--130. (Export to RIS)
FlyBase ID	FBrf0155962
Publication Type	Research paper
PubMed ID	12482966
PubMed Abstract	In a screen for Drosophila genes that interfere with transcriptional repression mediated by the Polycomb group of genes, we identified a dominant mutation affecting the Alhambra (Alh) gene, the fly homologue of the human AF10 gene. AF10 has been identified as a fusion partner of both MLL and CALM in infant leukemias. Both fusion proteins retain the leucine zipper domain of AF10 but not its PHD domain. We show here that, while the full-length ALH protein has no activity on Polycomb group-responsive elements (PREs), overexpression of the isolated ALH leucine zipper domain activates several PREs. Within the ALH full-length protein, the PHD domain inhibits the PRE deregulation mediated by the leucine zipper domain. This deregulation is conserved in the human AF10 leucine zipper domain, which confers the same activity on an oncogenic MLL-AF10 fusion protein expressed in Drosophila melanogaster. These data reveal new properties for the leucine zipper domain and thus might provide new clues to understanding the mechanisms by which AF10 fusion proteins in which the PHD domain is lost might trigger leukemias in humans.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Mol. Cell. Biol.
Title	Molecular and Cellular Biology
Publication Year	1981-
ISBN/ISSN	0270-7306
Data from Reference
Aberrations (2)
	Df(3R)Scx2 In(3R)Ubx^7LLats^R
Alleles (40)
	Alh::Hsap\MLL^{Scer\UAS.T:Zzzz\FLAG} Alh¹ Alh^{L.Scer\UAS.T:Zzzz\FLAG} Alh^L.Scer\UAS Alh^{LZ1.Scer\UAS.T:Zzzz\FLAG} Alh^{LZ2.Scer\UAS.T:Zzzz\FLAG} Alh^{PHD.L.Scer\UAS.T:Zzzz\FLAG} Alh^RV95 Alh^S.Scer\UAS Alh^unspecified Alh^y+ Alh^{Δ1-53.L.Scer\UAS.T:Zzzz\FLAG} Alh^{ΔLZ.L.Scer\UAS.T:Zzzz\FLAG} Alh^{ΔPHD.L.Scer\UAS.T:Zzzz\FLAG} Hsap\MLL::Hsap\MLLT10^{Scer\UAS.T:Zzzz\FLAG} Hsap\MLL^{Scer\UAS.T:Zzzz\FLAG} Hsap\MLLT10^LZ.Scer\UAS Mi-2⁴ mor¹ mor^LZ.Scer\UAS Pc¹⁶ ph-d⁵⁰⁴ ph-d⁵⁰⁵ ph-p⁵⁰⁴ ph-p⁵⁰⁵ ph-p^rIIA Psc¹ Psc^Arp1 Scer\GAL4^da.G32 Scer\GAL4^GMR.PFa Scer\UAS^5x.hs.SV40 Trl^R85 trx^E2 w¹¹¹⁸ w^+mC w^Fab-7.5F24 w^ph-p.lac+3 w^Scr.8.2X y^+mDint z¹
Constructs (23)
	P{da-GAL4.w^-} P{Fab7-w#un2} P{GAL4-da.G32} P{GMR-GAL4.w^-} P{lacW} P{SSRN+8.2Xb} P{UAS-Alh.FLAG} P{UAS-Alh.L} P{UAS-Alh.L-PHD} P{UAS-Alh.LZ1} P{UAS-Alh.LZ2} P{UAS-Alh.L-Δ1-53} P{UAS-Alh.L-ΔLZ} P{UAS-Alh.L-ΔPHD} P{UAS-Alh.S} P{UAS-lacZ.Abd-B.5F24} P{UAS-LZ-AF10} P{UAS-MLL.Nter} P{UAS-MLL-AF10} P{UAS-MLL-Alh} P{UAS-mor.LZ} P{UAST} P{UASy⁺}
Genes (21)
	Alh Alh::Hsap\MLL Fab-7 Hsap\MLL Hsap\MLL::Hsap\MLLT10 Hsap\MLLT10 Mi-2 mor Pc ph-d ph-p ph-PRE Psc Scer\GAL4 Scer\UAS T:Zzzz\FLAG Trl trx w y z
Insertions (5)
	P{}Alh¹ P{Fab7-w#un2}18.8.6 P{lacW.ph+3}ph-p^lac+3 P{lacW}3-76a P{lyB}Alh^y+