Transcription activation by Myc and Max: flanking sequences target activation to a subset of CACGTG motifs in vivo.

Fisher, Fernando; Crouch, Dorothy H.; Jayaraman, Padma-Sheela; Clark, W P; Gillespie, David A.; Goding, Colin R.

doi:10.1002/j.1460-2075.1993.tb06201.x

Cited by 92 publications

(76 citation statements)

References 39 publications

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“…In contrast, max(USF) failed to interact with any of the above preys (lines 17 ± 21). In keeping with previously reported observations using low copy number vectors Fisher et al, 1993), neither max nor max(USF) interacted with themselves (lines 3 and 16). These observations are consistent with the notion that mycmax and Mad-max heterodimerization is favored over max homodimerization.…”

Section: Characterization Of Max(usf)supporting

confidence: 90%

Lack of transcriptional repression by max homodimers

1998

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Max, a basic ± helix ± loop ± helix ± leucine zipper (bHLH-ZIP) protein, plays a central role in the transcriptional regulation of myc oncoprotein-responsive genes. Myc-max heterodimers bind to consensus E-box motifs near or within the promoters of these genes and activate gene expression, whereas heterodimers between max and members of the mad family of bHLH-ZIP proteins promote transcriptional repression. In contrast to all other members of the myc network, max readily homodimerizes and binds to identical E-box sites in vitro. However, the role for max homodimers in transcriptional repression in vivo is unclear. Upstream stimulatory factor (USF) is a bHLH-ZIP protein which does not interact with members of the myc-max-mad family. By replacing the HLH-ZIP domain of max with that from USF, we created a chimeric protein, max(USF), which was indistinguishable from max with respect to its ability to homodimerize and bind DNA. As expected, however, max(USF) was unable to heterodimerize with any of the tested max partner proteins and was incapable of suppressing c-myc target genes. Thus, transcriptional repression is an exclusive property of max-mad heterodimers and cannot be achieved by max homodimers alone.

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Section: Characterization Of Max(usf)supporting

confidence: 90%

Lack of transcriptional repression by max homodimers

1998

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“…However, subtle preferences, particularly for¯anking sequences, have been noted (Prendergast and Zi , 1991;Barrett et al, 1992;Fisher et al, 1993;Ma et al, 1993;Prochownik and VanAntwerp, 1993). Because very few in situ DNA binding sites for any of these proteins have been characterized (Grandori et al, 1996) and because the E-boxes of acknowledged cmyc transcriptional targets have not been examined for binding by N-myc and L-myc, it is not yet completely clear how in vitro binding site preferences might be related to those favored in vivo.…”

Section: Erential E Ects Of Myc Proteins On Dna Binding Transcripmentioning

confidence: 99%

MYC oncogenes and human neoplastic disease

1999

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c-myc, N-myc and L-myc are the three members of the myc oncoprotein family whose role in the pathogenesis of many human neoplastic diseases has received wide empirical support. In this review, we ®rst summarize data, derived mainly from non-clinical studies, indicating that these oncoproteins actually serve quite di erent roles in vivo. This concept necessarily lies at the heart of the basis for the observation that the deregulated expression of each MYC gene is reproducibly associated with only certain naturally occurring malignancies in humans and that these genes are not interchangeable with respect to their aberrant functional consequences. We also review evidence implicating each of the above MYC genes in speci®c neoplastic diseases and have attempted to identify unresolved questions which deserve further basic or clinical investigation. We have made every attempt to review those diseases for which signi®cant and con®rmatory evidence, based on studies with primary tumor material, exists to implicate MYC members in their causation and/or progression.

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“…A consensus sequence with the core 5'-CACGTG could be de®ned, which is referred to as Myc E box and evidence for additional preferred nucleotides¯anking the core sequence was obtained whereby the sequence 5'-GAC CACGTG GTC represents a high a nity binding site in vitro (Blackwell et al, 1990Halazonetis and Kadil, 1991;Kerkho et al, 1991;Fisher et al, 1993;Ma et al, 1993;Solomon et al, 1993;Sommer et al, 1998). The basic region of the bHLHZip domain makes base contacts and by this determines the speci®city of DNA binding (FerreÂ -D'AmareÂ et al, 1993;Brownlie et al, 1997; see also below).…”

Section: Structural Aspects Of the Bhlhzip Domainmentioning

confidence: 99%