The conserved Myc box 2 and Myc box 3 regions are important, but not essential, for Myc function in vivo

Schwinkendorf, Daniela; Gallant, Peter

doi:10.1016/j.gene.2009.02.009

Cited by 14 publications

(16 citation statements)

References 69 publications

(106 reference statements)

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“…1). The amino-terminal Hydra Myc1 domain exhibits less overall sequence identity to the human homolog, although Myc boxes I, II, IIIa, and IIIb, essential for Myc-induced cell transformation and transcriptional regulation (25)(26)(27)(28), display identities of 30.0%, 43.8%, 33.0%, and 41.7%, resp. The structures of Hydra Myc1 determined here and of the deduced Myc2 protein display the same principal topography and similar evolutionary relationship to the human protein ( Fig.…”

mentioning

confidence: 99%

Stem cell-specific activation of an ancestral myc protooncogene with conserved basic functions in the early metazoan Hydra

Hartl¹,

Mitterstiller

Valovka³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

142

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The c-myc protooncogene encodes a transcription factor (Myc) with oncogenic potential. Myc and its dimerization partner Max are bHLH-Zip DNA binding proteins controlling fundamental cellular processes. Deregulation of c-myc leads to tumorigenesis and is a hallmark of many human cancers. We have identified and extensively characterized ancestral forms of myc and max genes from the early diploblastic cnidarian Hydra, the most primitive metazoan organism employed so far for the structural, functional, and evolutionary analysis of these genes. Hydra myc is specifically activated in all stem cells and nematoblast nests which represent the rapidly proliferating cell types of the interstitial stem cell system and in proliferating gland cells. In terminally differentiated nerve cells, nematocytes, or epithelial cells, myc expression is not detectable by in situ hybridization. Hydra max exhibits a similar expression pattern in interstitial cell clusters. The ancestral Hydra Myc and Max proteins display the principal design of their vertebrate derivatives, with the highest degree of sequence identities confined to the bHLH-Zip domains. Furthermore, the 314-amino acid Hydra Myc protein contains basic forms of the essential Myc boxes I through III. A recombinant Hydra Myc/Max complex binds to the consensus DNA sequence CACGTG with high affinity. Hybrid proteins composed of segments from the retroviral v-Myc oncoprotein and the Hydra Myc protein display oncogenic potential in cell transformation assays. Our results suggest that the principal functions of the Myc master regulator arose very early in metazoan evolution, allowing their dissection in a simple model organism showing regenerative ability but no senescence.cell proliferation | cnidaria | development | transcription factor

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mentioning

confidence: 99%

Stem cell-specific activation of an ancestral myc protooncogene with conserved basic functions in the early metazoan Hydra

Hartl¹,

Mitterstiller

Valovka³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

142

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“…In addition, this regime also produces necrotic patches and dissociation of the dorsal and ventral wing surfaces, presumably as a consequence of Myc-driven apoptosis and ef- fects on cell-cell adhesion (Ref. 28 and Fig. 3B).…”

Section: Dhcf Is Important For the Expression Of Myc Targets In Cul-mentioning

confidence: 96%

“…It has previously been shown that overexpression of Myc in the developing eye (under the control of GMR-GAL4) results in larger adult ommatidia, reflecting the growth-promoting ability of Myc (8,12,28). Overexpression of dHCF under the same regime has no effect on ommatidial size.…”

Section: Dhcf Is Important For the Expression Of Myc Targets In Cul-mentioning

confidence: 99%

Drosophila Myc Interacts with Host Cell Factor (dHCF) to Activate Transcription and Control Growth

Furrer

Balbi²,

Albarca-Aguilera³

et al. 2010

Journal of Biological Chemistry

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The Myc proto-oncoproteins are transcription factors that recognize numerous target genes through hexameric DNA sequences called E-boxes. The mechanism by which they then activate the expression of these targets is still under debate. Here, we use an RNAi screen in Drosophila S2 cells to identify Drosophila host cell factor (dHCF) as a novel co-factor for Myc that is functionally required for the activation of a Myc-dependent reporter construct. dHCF is also essential for the full activation of endogenous Myc target genes in S2 cells, and for the ability of Myc to promote growth in vivo. Myc and dHCF physically interact, and they colocalize on common target genes. Furthermore, down-regulation of dHCF-associated histone acetyltransferase and histone methyltransferase complexes in vivo interferes with the Myc biological activities. We therefore propose that dHCF recruits such chromatin-modifying complexes and thereby contributes to the expression of Myc targets and hence to the execution of Myc biological activities.Myc genes were identified for their powerful transforming capabilities in vertebrate systems and later shown to be essential for normal development (reviewed in Refs. 1, 2). The molecular functions of Myc are evolutionarily conserved, and the single Myc homolog in Drosophila melanogaster (called Myc when referring to the protein, and diminutive or dm when referring to alleles) can substitute for vertebrate Myc (3) and vice versa (Ref. 4, for a recent review see Ref. 5). Drosophila Myc prominently controls cellular growth; null mutations prevent organismal growth and lead to death during early larval stages (6), whereas hypomorphic dm mutations prolong development and result in small adult flies, made up of smaller than wild-type cells (7). Conversely, overexpression of Myc results in bigger cells, but also stimulates apoptosis (7,8). These effects of Myc are mediated by the transcriptional regulation of a large number of target genes (9, 10), including genes transcribed by RNA polymerases I (11) and III (12).

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“…Numbered deletions (created by site-directed mutagenesis) retain the indicated regions of the Myc protein, e.g., amino acids 403-717. Mutants lacking specific Myc domains have been described previously (18,28,33). In brief, they carry the following modifications: ΔN-term lacks amino acids 1-293, ΔMB2 has the amino acid "GP" instead of amino acids 68-84 (Myc box 2), ΔMB3 has amino acid "F" instead of amino acids 405-422 (Myc box 3), ΔC-term lacks amino acids 626-717 (C terminus: bHLHZ), and ΔZ lacks amino acids 676-717 (leucine zipper).…”

Section: Included Gmr-gal4 Uas-gfp Uas-lacz Gmr-gal4 Uas-gfp Uasleo1mentioning

confidence: 99%

“…In addition, the MBIIIb region is highly conserved in Drosophila Myc, but a mutant Myc derivative lacking the entire region can substitute for wild-type Myc in null mutant flies (18). Additional recruitment factors might include various sequence-specific transcription factors with which Myc has been reported to associate (notably Miz1, Sp1, NF-Y, Smad2/3, and YY1; reviewed in ref.…”

mentioning

confidence: 99%

PAF1 complex component Leo1 helps recruit Drosophila Myc to promoters

Gerlach

Furrer

Gallant

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The Myc oncogene is a transcription factor with a powerful grip on cellular growth and proliferation. The physical interaction of Myc with the E-box DNA motif has been extensively characterized, but it is less clear whether this sequence-specific interaction is sufficient for Myc's binding to its transcriptional targets. Here we identify the PAF1 complex, and specifically its component Leo1, as a factor that helps recruit Myc to target genes. Since the PAF1 complex is typically associated with active genes, this interaction with Leo1 contributes to Myc targeting to open promoters.

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The conserved Myc box 2 and Myc box 3 regions are important, but not essential, for Myc function in vivo

Cited by 14 publications

References 69 publications

Stem cell-specific activation of an ancestral myc protooncogene with conserved basic functions in the early metazoan Hydra

Stem cell-specific activation of an ancestral myc protooncogene with conserved basic functions in the early metazoan Hydra

Drosophila Myc Interacts with Host Cell Factor (dHCF) to Activate Transcription and Control Growth

PAF1 complex component Leo1 helps recruit Drosophila Myc to promoters

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