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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The c-myc protein (Myc) contains an amino-terminal transcriptional activation domain and a carboxy-terminal basic helix-loop-helix-leucine zipper (bHLH-Z) domain that directs dimerization of Myc with its partner, the max protein (Max), and promotes DNA binding to sites containing a CACGTG core consensus sequence. Despite these characteristics and the observation that Myc can modulate gene expression, a direct role for Myc or Max as transcription factors has never been demonstrated. Here we use Saccharomyces cerevisiae as an in vivo model system to show that the Myc protein is a sequence-specific transcriptional activator whose DNA binding is strictly dependent on dimerization with Max. Transactivation is mediated by the amino-terminal domain of Myc. We find that Max homodimers bind to the same DNA sequence as Myc+Max but that they fail to transactivate and thus can antagonize Myc+Max function. We also show that the Max HLH-Z domain has a higher affinity for the Myc HLH-Z domain than for itself, and suggest that the heterodimeric Myc+Max activator forms preferentially at equilibrium.
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PMID:Transcriptional activation by the human c-Myc oncoprotein in yeast requires interaction with Max. 140 55

The Max protein forms a heterodimeric complex with the Myc family of proteins and binds to DNA in a sequence-specific manner. We investigated the role of the helix-loop-helix (HLH), leucine zipper (LZ) and basic domains of Max in protein complex formation, DNA-binding activity and transcriptional regulation. We mutagenized the basic, HLH and LZ domains of Max and studied the ability of the normal and mutant proteins to bind to DNA as both homo- and heterodimers and their ability to heterodimerize with Myc. Helix-1 and helix-2 regions of Max were found to be critical for homodimer formation and subsequent DNA binding, while the LZ was essential for heterodimer formation. In transient transfection assays the Myc protein functioned as a transcriptional activator while Max protein repressed the trans-activation observed with Myc.
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PMID:Mutational analysis of Max: role of basic, helix-loop-helix/leucine zipper domains in DNA binding, dimerization and regulation of Myc-mediated transcriptional activation. 140 52

c-Myc is a cellular onco-protein and a transcriptional activator important for cell growth, cell division, and tumorigenesis. Despite all that is known of its function, the mechanism of how c-Myc contributes to tumorigenesis is unclear. To gain insight into the mechanism through which c-Myc protein exerts its oncogenic activity, we performed large-scale, tandem repeat affinity purification and identified the F box only protein 8 (FBX8), an F-box- and Sec7 domain-containing protein, as a novel Myc-binding protein. The c-Myc/FBX8 interaction was mediated by the c-Myc box II (MBII) region. We also confirmed that Myc protein overexpression in 293T cells affected FBX8 cellular translocation and led to recovery from FBX8-mediated inhibition of ADP-ribosylation factor 6 (ARF6) function during cell invasion. Together, these results suggest that FBX8 is a novel c-Myc binding protein and that c-Myc induces cell invasive activity through the inhibition of FBX8 effects on ARF6 function during cell invasion.
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PMID:c-Myc stimulates cell invasion by inhibiting FBX8 function. 2084 31

The (c-)Myc oncoprotein and its cousins, the N-Myc and L-Myc proteins, show all hallmarks of transcriptional activator proteins: Myc carries a carboxy-terminal DNA binding domain, which mediates sequence-specific binding to DNA. At its amino-terminus, Myc carries a transcriptional regulatory domain that strongly activates transcription when fused to an ectopic DNA binding domain; moreover, the strength of activation of different members of the Myc family correlates with their ability to transform rodent cells. Furthermore, activation of conditional alleles of Myc, either tetracycline or estrogen inducible, upregulates expression of a large number of genes, both in tissue culture and in transgenic animals. Indeed, many of these genes have essential roles in cell proliferation, cell growth, and metabolism; two of them, odc, encoding ornithine decarboxylase, a rate-limiting enzyme of polyamine biosynthesis, and rpl24, encoding a constituent of the large ribosomal subunit, are haploinsufficient for Myc-induced lymphomagenesis but not for normal development, arguing very strongly that upregulation of both genes is critical for Myc-dependent tumor formation. Undoubtedly, therefore, Myc exerts part of its biological activities via transcriptional upregulation of a large number of target genes. One of the key issues in the field is whether there are additional biochemical activities of the Myc protein and, if so, whether and how they contribute to Myc biology. This review summarizes evidence demonstrating that Myc has the ability to repress transcription and that this may be an important function during oncogenic transformation.
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PMID:Transcriptional repression: the dark side of myc. 2177 59