Colocalization of the myc Oncogene Protein and Small Nuclear Ribonucleoprotein Particles

Sullivan, N F; Watt, Rosemary; Delannoy, Mélanie; Green, C.L.; Spector, D. L.

doi:10.1101/sqb.1986.051.01.107

Cited by 11 publications

(4 citation statements)

References 22 publications

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“…While one early report of Myc localization described a dispersed granular appearance which may be consistent with our results [Hann et al, 1983], a later study reported that c-Myc colocalized with small nuclear ribonucleoprotein (snRNP) particles in nuclear speckles, also termed SC35 domains [Sullivan et al, 1986;Spector et al, 1987]. A recent paper investigated the localization of Myc and the Myc-interacting proteins Mad and Max by expression of transiently transfected GFP-tagged chimeric proteins [Yin et al, 2001].…”

Section: Discussionsupporting

confidence: 85%

“…The Myc signal typically avoided (or was reduced in) the nucleolus. We found no evidence for c-Myc association with splicing factor rich SC-35 domains, as early observations with endogenous Myc antibodies had indicated [Sullivan et al, 1986;Spector et al, 1987]. Our consistent findings of a dispersed nucleoplasmic distribution for Myc are especially important in light of two recent reports that localized transiently-expressed, GFP-tagged Myc to a prominent nuclear spotted pattern (not overlapping SC35 domains) [Yin et al, 2001] versus a more uniform dispersed pattern [Arabi et al, 2003] (see Discussion).…”

Section: In Situ Localization Of C-myc Proteincontrasting

confidence: 48%

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c‐Myc localization within the nucleus: Evidence for association with the PML nuclear body

Smith

Byron

O’Connell

et al. 2004

J of Cellular Biochemistry

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Definitive localization of c-Myc within the nucleus is important to fully understand the regulation and function of this oncoprotein. Studies of c-Myc distribution, however, have produced conflicting results. To overcome technical challenges inherent in c-Myc cytology, we use here three methods to visualize c-Myc and in addition examine the impact of proteasome inhibition. EYFP or HA-tagged Myc was reintroduced by stable transfection into myc null diploid rat fibroblasts, replacing endogenous Myc with tagged Myc expressed at or near normal levels. This tagged Myc is shown to functionally replace the endogenous Myc by restoration of normal cell morphology and growth rate. We were able to confirm key findings using antibodies to the endogenous c-Myc and/or its partner, Max. Contrary to some published reports, by all three methods the c-Myc protein in rat fibroblasts distributes predominantly throughout the nucleus in a dispersed granular pattern, avoiding the nucleolus. Importantly, however, several findings provide evidence for an unanticipated relationship between c-Myc and PML nuclear bodies, which is enhanced under conditions of proteasome inhibition. Evidence of Max concentration within PML bodies is shown both with and without proteasome inhibition, strengthening the relationship between PML bodies and Myc/Max. Some accumulation of Myc and Max in nucleoli upon proteasome inhibition is also observed, although co-localization of ubiquitin was only seen with PML bodies. This work provides a comprehensive study of c-Myc distribution and also presents the first evidence of a relationship between turnover of this oncoprotein and PML nuclear bodies, known to break down in certain cancers.

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Section: Discussionsupporting

confidence: 85%

Section: In Situ Localization Of C-myc Proteincontrasting

confidence: 48%

c‐Myc localization within the nucleus: Evidence for association with the PML nuclear body

Smith

Byron

O’Connell

et al. 2004

J of Cellular Biochemistry

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“…In somatic cells, c-MYC has been shown to be localized in nuclear speckles containing various splicing factors [22,23]. Furthermore, the distribution of speckles in somatic cells is very similar to that of the c-MYC granules in GOs and preimplantation embryos [24].…”

Section: Localization Of C-myc In Nuclear Specklesmentioning

confidence: 82%

Expression of c-MYC in Nuclear Speckles During Mouse Oocyte Growth and Preimplantation Development

Suzuki

Abe

Inoue

et al. 2009

Journal of Reproduction and Development

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Abstract. Myelocytomatosis oncogene (c-myc) is a major transcriptional regulator that controls various biological processes, and its deregulated expression causes carcinogenesis. To investigate the involvement of c-myc in oogenesis and preimplantation development, the expression of c-MYC during these stages was examined by immunocytochemistry. A strong c-MYC signal was detected in the nucleus of growing and fully grown oocytes as well as in preimplantation embryos before the morula stage. The signal intensity decreased slightly at the morula stage, and no signal was detected in blastocysts. Close observation of the nucleus revealed that c-MYC was localized in small granules that appeared to be nuclear speckles controlling pre-mRNA splicing. Although the number of granules decreased during oocyte growth, their size increased. After fertilization, the granules of c-MYC disappeared from the pronuclei, and c-MYC was evenly distributed in the nucleoplasm at the 1-cell stage, but the granules reappeared at the 2-cell stage. These results suggest that c-myc is involved in oocyte growth and preimplantation development and that its role changes during these stages. . It is ubiquitously expressed in normal tissues, but in some tumor cells, its expression is highly elevated or deregulated [2,3]. While this overexpression is not sufficient for induction of oncogenic transformation, it contributes to the process [4,5]. In normal cells, c-myc plays various important roles in cell survival, including transcriptional regulation, and the gene product, c-MYC protein contains both a leucine zipper and helix-loop-helix motifs, which allow it to bind to specific target sequences [6][7][8]; moreover, it forms a heterodimer with a protein called MAX, which is necessary for DNA binding, leading to the up-or downregulation of target gene transcription [9]. In addition, c-MYC is involved in DNA replication via a mechanism that does not involve transcriptional activation [10]. The suppression of c-myc expression by antisense RNA or specific antibodies inhibits DNA synthesis [11,12]. Furthermore, c-myc is involved in various other cellular functions, such as chromatin modification, apoptosis, and differentiation [13].C-MYC is an essential factor for normal embryonic development and differentiation. For example, suppression of c-MYC expression by antisense oligonucleotides reduces the developmental rate at the blastocyst stage in vitro [14], and a null mutation in cmyc results in embryonic lethality before day 10.5 in vivo [15]. However, the role of c-myc in oogenesis and early preimplantation development remains to be elucidated. Although c-myc RNA has been shown to be expressed during oocyte growth and preimplantation development, no data exist regarding the expression of c-MYC during these stages. In oocytes and early preimplantation embryos, the expression patterns of certain proteins are different from those of the transcripts, since the translation of maternal mRNA is posttranscriptionally regulated in a complex manner [16,17].In the ...

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“…The localization of N-myc:,-gal#3 protein may demonstrate for the first time the actual sites at which N-myc proteins carry out their functions. It is interesting to note that Sullivan et al (20) observed a "speckled pattern" of c-myc and v-myc protein distribution in a nucleus by using specific antibodies.…”

mentioning

confidence: 99%

Subnuclear localization and antitransforming activity of N-myc:beta-galactosidase fusion proteins.

1988

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N-myc expression is under stage-and tissue-specific regulation in mammalian development, but its function is totally unknown. We sought agents to block N-myc activity in order to infer from the effect the possible function of N-myc in the apparently complex processes. As candidates for such agents, we tested fusion genes encoding N-myc:1-galactosidase fusion proteins for their effects on the formation of transformed foci of rat embryo primary fibroblasts as the result of transfection with N-myc and activated H-ras. One of the gene constructs very efficiently antagonized N-myc activity, as assessed by its effect on focus formation, but did not appreciably affect cell viability. The product of this gene was not only targeted to the nucleus but also accumulated in subnuclear loci which may represent the sites where normal N-myc proteins reside. The occurrence of antagonistic effect at a low stoichiometric ratio suggested that the fusion protein gene competed with the N-myc gene in a fashion analogous to a dominant negative mutation.

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Colocalization of the myc Oncogene Protein and Small Nuclear Ribonucleoprotein Particles

Cited by 11 publications

References 22 publications

c‐Myc localization within the nucleus: Evidence for association with the PML nuclear body

c‐Myc localization within the nucleus: Evidence for association with the PML nuclear body

Expression of c-MYC in Nuclear Speckles During Mouse Oocyte Growth and Preimplantation Development

Subnuclear localization and antitransforming activity of N-myc:beta-galactosidase fusion proteins.

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