Association of c‐myc protein with enzymes of DNA replication in high molecular weight fractions from mammalian cells

Studzinski, George P.; Shankavaram, Uma; Moore, Dorothy C.; Reddy, Prashanti

doi:10.1002/jcp.1041470305

Cited by 11 publications

(6 citation statements)

References 48 publications

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“…Other studies performed with transformed cells show that c-Myc can also associate with high-molecularmass complexes. Using cross-linking experiments, Gillespie and Eisenman (24) found a 500-kDa complex (15S), whereas Studzinski et al (74) reported an association of c-Myc with a 600-kDa complex (around 17S). The selective and rapid nuclear entry of only one of the two c-Myc species led us to search for the possible association of c-Myc with protein complexes unique to early development.…”

Section: Resultsmentioning

confidence: 99%

Selective and Rapid Nuclear Translocation of a c-Myc-Containing Complex after Fertilization of Xenopus laevis Eggs

Lemaı̂tre

Bocquet

Buckle

et al. 1995

Molecular and Cellular Biology

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We report here unusual features of c-Myc specific to early embryonic development in Xenopus laevis, a period characterized by generalized transcriptional quiescence and rapid biphasic cell cycles. Two c-Myc protein forms, p61 and p64, are present in large amounts in the oocyte as well as during early development. In contrast, only p64 c-Myc is present in Xenopus somatic cells. p61 c-Myc is the direct translation product from both endogenous c-myc mRNAs and c-myc recombinant DNA. It is converted to the p64 c-Myc form after introduction into an egg extract, in the presence of phosphatase inhibitors. p61 and p64 belong to two distinct complexes localized in the cytoplasm of the oocyte. A 15S complex contains p64 c-Myc, and a 17.4S complex contains p61 c-Myc. Fertilization triggers the selective and total entry of only p64 c-Myc into the nucleus. This translocation occurs in a nonprogressive manner and is completed during the first cell cycles. This phenomenon results in an exceptionally high level of c-Myc in the nucleus, which returns to a somatic cell-like level only at the end of the blastulation period. During early development, when the entire embryonic genome is transcriptionally inactive, c-Myc does not exhibit a DNA binding activity with Max. Moreover, embryonic nuclei not only prevent the formation of c-Myc/Max complexes but also dissociate such preformed complexes. These peculiar aspects of c-Myc behavior suggest a function that could be linked to the rapid DNA replication cycles occurring during the early cell cycles rather than a function involving transcriptional activity.A great deal of evidence has accumulated indicating a role for the nuclear protein c-Myc in a variety of cellular processes such as proliferation, mitogenesis, differentiation, and apoptosis (21, 50, 51). c-Myc is required for normal cell cycle progression (64, 68). Cells that express high levels of c-Myc generally exhibit reduced requirements for growth factors (2, 43, 70, 71) and exhibit higher growth rates (43, 59), characterized by a shortened G 1 phase (35). The expression of c-Myc can also overcome growth arrest (2, 41). In contrast, exit from the cell cycle or entry into the differentiation process requires downregulation of c-Myc expression (30,32,62,70). Recently a possible role for c-Myc during the G 2 phase of the cell cycle has also been suggested (67,68).At the molecular level, most recent evidence indicates that c-Myc is directly involved in the regulation of transcription. The c-myc gene encodes nuclear phosphoproteins containing three distinct domains. The COOH terminus includes a basic region followed by a helix-loop-helix leucine zipper (bHLHZip) domain, involved in sequence-specific DNA binding and protein-protein interaction, respectively (5). The NH 2 -terminal domain of c-Myc is required for transformation (73) and has been shown to function as a transcriptional activation domain (36) able to contact the TATA-binding protein (29). Heterodimers of c-Myc and the bHLH-Zip protein Max specifically bind to the E-box s...

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Section: Resultsmentioning

confidence: 99%

Selective and Rapid Nuclear Translocation of a c-Myc-Containing Complex after Fertilization of Xenopus laevis Eggs

Lemaı̂tre

Bocquet

Buckle

et al. 1995

Molecular and Cellular Biology

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“…However, there is evidence which suggests that c-myc may also function in the latter half of G1 and perhaps during S phase (7,46,47). Although controversial, it has been reported that the c-Myc protein has been detected in several cell types in high molecular weight complexes containing DNA polymerase a and several other enzymes necessary for DNA replication (47). These data might suggest a functional role for the c-Myc protein in late-G1 complexing prior to the onset of S phase as well as during the replicative phase itself.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of the c-Myc oncoprotein blocks the growth-inhibitory response but is required for the mitogenic effects of transforming growth factor beta 1.

Alexandrow

Kawabata

Aakre

et al. 1995

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

131

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“…This transcription function of ORC1 has also been suggested by experimental systems in yeast and Drosophila [16–20]. In addition to the role of c‐Myc as a transcription factor, an earlier study also showed that c‐Myc is co‐fractionated with DNA replication proteins in human HeLa cells [21]. Proof of a replication role of c‐Myc, however, has not been obtained.…”

Section: Introductionmentioning

confidence: 83%

CDC6 interacts with c‐Myc to inhibit E‐box‐dependent transcription by abrogating c‐Myc/Max complex

et al. 2000

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The c-myc oncogene product (c-Myc) is a transcription factor that dimerizes with Max and recognizes the E-box sequence. It plays key functions in cell proliferation, differentiation and apoptosis. It is generally thought that c-Myc transactivates genes encoding proteins essential to cell-cycle progression by binding to the E-boxes that control them. The functions of c-Myc are also thought to be modulated by its associated proteins, several of which have recently been identified. In this study, we found that c-Myc directly bound in vivo and in vitro to the N-terminal region of human CDC6, a component of the pre-replication complex, and that both colocalized in cell nuclei. CDC6 bound to the C-proximal region of c-Myc, thereby competing with Max on the E-box sequence and changing c-Myc/Max heterodimer to a Max/Max homodimer. In consequence, the E-box-dependent transcription activity of cMyc was abrogated. These results suggest that, in addition to its DNA replication activity, CDC6 also has a role as a transcriptional suppressor of c-Myc. ß

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Association of c‐myc protein with enzymes of DNA replication in high molecular weight fractions from mammalian cells

Cited by 11 publications

References 48 publications

Selective and Rapid Nuclear Translocation of a c-Myc-Containing Complex after Fertilization of Xenopus laevis Eggs

Selective and Rapid Nuclear Translocation of a c-Myc-Containing Complex after Fertilization of Xenopus laevis Eggs

Overexpression of the c-Myc oncoprotein blocks the growth-inhibitory response but is required for the mitogenic effects of transforming growth factor beta 1.

CDC6 interacts with c‐Myc to inhibit E‐box‐dependent transcription by abrogating c‐Myc/Max complex

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