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PubMed1990

Prolonged N-myc protein half-life in a neuroblastoma cell line lacking N-myc amplification.

Genomic amplification of the oncogene N-myc is associated with rapid tumor progression and poor prognosis in patients with neuroblastoma (NB). However, 40% of NBs which lack N-myc amplification are also clinically aggressive. Factors other than N-myc copy number must therefore play a role in determining tumor progression in these NBs. We have established an unusual human NB cell line (NBL-S) from the primary tumor of a patient with rapidly progressive disease which lacks N-myc amplification. The doubling time in vitro (48 h) and the time from injection of 2 x 10(7) cells to detectable tumors in nude mice (46 days) in similar to NB cell lines with amplified N-myc. However, karyotype analysis reveals no evidence of double minutes (DMs), homogeneously staining regions (HSRs), or chromosome 1p deletions, features commonly seen in NB cell lines. The cells have the cell surface phenotype typical of N-myc amplified NB (HLA-A,B,C negative and HSAN 1.2 positive), and similar to other NB cell lines, N-myc RNA and protein are expressed. Interestingly, the half-life of the N-myc protein in NBL-S is prolonged (approximately 100 min) compared to the short N-myc protein half-life previously described in N-myc amplified NB cell lines (approximately 30 min). Because N-myc protein is thought to have a regulatory role, prolongation of the half-life of this protein may be an important factor in the regulation of growth in NBs which lack N-myc amplification and rapidly progress.

Animals↗
PubMed1987

Immunologic competence of B cells subjected to constitutive c-myc oncogene expression in immunoglobulin heavy chain enhancer myc transgenic mice.

B cell activation is associated with a marked transient rise in expression of the c-myc proto-onco-gene. A unique opportunity to examine the effects of constitutive c-myc expression upon B cell function is provided by transgenic mice in which the c-myc oncogene is regulated by the enhancer (E mu) from the immunoglobulin locus (E mu-myc mice). We have examined the immunologic competence of B cells from E mu-myc mice both in vitro and in vivo. Upon stimulation, many E mu-myc B cells can proliferate to form clones most of which contain antibody-forming cells. However, the frequency of responsive B cells from E mu-myc donors is only about 30% that of B cells from normal littermates. Thus, enforced myc expression is not sufficient to block the differentiation of all B cells, but a much larger fraction of the immunoglobulin-bearing cells from E mu-myc mice are incompetent. Upon immunization, E mu-myc mice mounted specific antibody responses, although some responses were delayed. Isotype switching can occur, since we observed hemolytic plaques of both IgM and IgG type and detected specific antibody of both classes in the serum. Moreover, the serum from nonimmunized E mu-myc mice contained normal levels of both IgM and IgG. Thus constitutive expression of the c-myc gene appears to retard B cell differentiation, but does not grossly impair immunologic function in the intact animal.

Animals↗
PubMed1989

Lymphomagenesis in Emu-myc transgenic mice does not require transgene rearrangement or mutation of myc exon 1.

In most human Burkitt's lymphomas, translocation of the myc oncogene to an immunoglobulin locus is associated with loss of myc exon 1 or with mutations near its 3' border, a region where myc transcription is attenuated and translation of a larger myc polypeptide initiates. Emu-myc transgenic mice, which bear the three myc exons coupled to an immunoglobulin enhancer, provide a model for the development of such lymphomas, because their lymphomagenesis appears to require events other than expression of the transgene. To determine whether myc rearrangement or exon 1 mutation is a necessary tumorigenic event, we examined the transgene structure and myc exon 1 sequences in Emu-myc B lymphoid tumours. Southern blots revealed no transgene rearrangements in 20 of the lymphomas, and only two tumours showed amplification (2 to 5-fold). To search for exon 1 alterations, the exon 1 mRNA region was amplified from five tumours by polymerase chain reaction and sequenced, but no mutations were found. Hence, neither excision nor mutation of exon 1 is necessary to render myc tumorigenic. The sequence analysis across the exon 1-exon 2 boundary unexpectedly revealed an ambiguity in myc splicing that predicts a variant form of the larger myc polypeptide lacking a single amino acid residue.

Amino Acid Sequence↗
PubMed1987

A sensitive and quantitative enzyme-linked immunosorbence assay for the c-myc and N-myc oncoproteins.

The c-myc and N-myc nuclear oncoproteins are implicated in the genesis and maintenance of the transformed phenotype in several types of neoplastic disease, and the c-myc protein is involved in the progression of normal cells through the cell cycle. We have designed and developed sensitive and quantitative ELISAs for these proteins. Myc proteins are captured from cell lysates by an antibody directed against a peptide sequence substantially conserved in all known myc proteins; the captured proteins are recognised by a specific anti-c-myc or anti-N-myc monoclonal antibody conjugated to alkaline phosphatase; bound alkaline phosphatase is measured with an extremely sensitive cycling enzyme system that generates a coloured end-product. The c-myc assay is calibrated using bacterially expressed human c-myc protein. We have used this assay to estimate the number of c-myc molecules in a range of normal and transformed cells of human, murine, and feline origin; to monitor increases in c-myc expression when quiescent cells are stimulated with growth factors; and to follow the decrease in c-myc protein levels when HL60 promyelocytic leukaemia cells are induced to differentiate with dimethylsulphoxide or phorbol esters.

Animals↗
PubMed1993

Retroviral enhancer insertion 5' of c-myc in two translocation-negative mouse plasmacytomas upregulates c-myc expression to different extents.

Essentially all murine plasmacytomas have deregulated c-myc expression that is typically brought about by chromosomal translocations between the c-myc/Pvt-1 locus and one of the immunoglobulin loci. ABPC 22 and RFPC 2782 are BALB/c plasmacytomas that lack chromosomal translocations yet have Southern blot evidence of c-myc gene rearrangements. In this report we show that proviral integrations 5' of the c-myc gene can deregulate c-myc expression in mouse plasmacytomas. Analysis of DNA sequences 5' of the c-myc genes from both tumors demonstrated that rearrangements were caused by retroviral integrations 5' of c-myc exon 1. The proviral insertion in RFPC 2782 was associated with a high steady-state c-myc mRNA level comparable to that seen in plasmacytomas with typical translocations. An analogous proviral insertion in ABPC 22 was associated with a c-myc RNA level that was only 38% of that of RFPC 2782. Nuclear run-on studies of c-myc transcription showed that ABPC 22 has both a lower rate of transcription and a greater degree of transcriptional attenuation than RFPC 2782. DNA sequencing of the long terminal repeat of each tumor provirus showed that the ABPC 22 provirus harbors a deletion of one of the two direct repeats in the viral enhancer, whereas both repeats are present in the RFPC 2782 provirus. These data indicate that maximum LTR enhancer effectiveness in plasmacytomas in vivo requires the presence of both LTR direct repeats. The documentation of the low level of steady-state c-myc mRNA in ABPC 22 supports the notion that deregulated c-myc expression, even at low steady state levels, is effective in supporting the development of plasmacytomas.

Animals↗
PubMedDate not supplied

A polyclonal antibody against synthetic peptide conserved in N-Myc protein reacts with water-soluble recombinant N-Myc protein.

The importance of determining the N-Myc protein has been emphasized in neuroblastoma. We attempted to obtain a water-soluble N-Myc protein, and an antibody highly specific for the N-Myc protein. A plasmid was constructed from partial exons 2 and 3 of the N-myc gene, and expressed in Escherichia coli by isopropyl-beta,-D-thiogalactopyranoside. Newly obtained N-Myc (rN-Myc) was water-soluble with a M.W. of 38 kDa. An N-Myc-specific peptide, GVAPPRPGG RQTSGGDH, was used to raise an antibody. Specificity of the obtained antibody was confirmed and we found the rN-Myc protein reacts positively with the anti-N-Myc IgG raised here. The rN-Myc protein and the anti-N-Myc IgG obtained are expected to be used in an ELISA for N-Myc.

Amino Acid Sequence↗
PubMed1982

Isolation and characterization of c-myc, a cellular homolog of the oncogene (v-myc) of avian myelocytomatosis virus strain 29.

The chicken genome contains nucleotide sequences homologous to transforming genes (oncogenes) of a number of avian retroviruses. We have isolated chicken DNA (c-myc) that is homologous to the oncogene (v-myc) of the avian myelocytomatosis virus MC29 and have compared the structures of the cellular and viral genes. Results from restriction endonuclease mapping of c-myc and from analysis of heteroduplexes between the DNAs of the cellular and viral genes show that c-myc is homologous to 1,500 nucleotides in v-myc DNA. This homologous region is interrupted in c-myc by an intron-like sequence of 1,100 nucleotides which is absent from v-myc. Nuclear RNA from normal chicken cells contains at least five species of transcripts from c-myc ranging from 2.5 to 6.5 kilobases in length. By contrast, cytoplasm contains only the 2.5-kilobase c-myc RNA. These features of the c-myc gene and its nuclear transcripts are characteristic of normal cellular genes and suggest that the myc gene is of cellular rather than viral origin. The exons in c-myc may define two functional domains in the gene and may therefore facilitate the dissection of the different oncogenic potentials of the MC29 virus.

Animals↗
PubMed1990

[Expression of c-myc and N-myc in mouse embryos during craniofacial development].

To analyze the role of c- and N-myc on the craniofacial development during the midgestation of mouse embryo, the temprospatial expression in the mandible and the tooth germ was examined by in situ hybridization. In the mandible, c-myc RNA was strongly expressed in the mesenchymal condensation surrounding the ossification center in which a high-level expression of osteopontin was detected with the basal-level expression of c-myc in the corresponding area. In tooth germs, the strong expression of c-myc was detected uniformly in the epithelia of bud stage and then gradually localized in the inner enamel epithelia from cap to bell stages. In contrast, the expression of N-myc was weakly detected in the undifferentiated mesenchymal cells of the dental papilla but was not detected in the regions where c-myc was highly expressed. To study the correlation of myc expression and growth activity, the incorporation of BrdU was examined immunohistochemically. The results revealed that levels of BrdU incorporation were similar between the regions where c-myc was highly expressed and the regions where basal-levels of c- and N-myc expression were detected, suggesting that levels of myc expression are not necessarily correlated to the growth activity. These results indicated that c- and N-myc genes are differentially expressed and further raise the possibility that c- and N-myc may play a major role in differentiation rather than proliferation in the early stage of these organogenesis.

Animals↗
PubMed2001

Contrasting localization of c-Myc with other Myc superfamily transcription factors in the human hair follicle and during the hair growth cycle.

The mammalian hair follicle is a highly dynamic skin appendage that undergoes repeated cycles of growth and regression, involving closely co-ordinated regulation of cell proliferation, differentiation, and apoptosis. The Myc superfamily of transcription factors have been strongly implicated in the regulation of these processes in many tissues. Using immunohistochemistry, we have investigated the patterns of c-Myc, N-Myc, Max, and Mad1-4 expression at different stages of the human hair growth cycle. N-Myc, Max, Mad1, and Mad3 immunoreactivity was detected in the epidermis and the epithelium of both anagen and telogen hair follicles. Three distinct patterns of hair follicle c-Myc immunoreactivity were observed. In the infundibulum, c-Myc staining was predominantly in the basal layers, with little detectable immunoreactivity in the terminally differentiating suprabasal layers; this pattern was similar to that seen in the epidermis. In contrast, c-Myc expression in the follicle bulb was found both in the proliferating germinative epithelial cells and in the terminally differentiating matrix cells that give rise to the hair fiber. Finally, intense c-Myc immunoreactivity was detected in the bulge region of the outer root sheath. Using the C8/144B antibody as a bulge marker, we confirmed that c-Myc immunoreactivity in the outer root sheath correlates with the putative hair follicle stem cell compartment. c-Myc expression in the bulge was independent of the hair growth cycle stage. Our data suggest that Myc superfamily members serve different functions in separate epithelial compartments of the hair follicle and may play an important role in determining cell fate within the putative stem cell compartment.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed1999

Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize Myc.

The human proto-oncogene c-myc encodes a highly unstable transcription factor that promotes cell proliferation. Although the extreme instability of Myc plays an important role in preventing its accumulation in normal cells, little is known about how Myc is targeted for rapid destruction. Here, we have investigated mechanisms regulating the stability of Myc. We show that Myc is destroyed by ubiquitin-mediated proteolysis, and define two elements in Myc that oppositely regulate its stability: a transcriptional activation domain that promotes Myc destruction, and a region required for association with the POZ domain protein Miz-1 that stabilizes Myc. We also show that Myc is stabilized by cancer-associated and transforming mutations within its transcriptional activation domain. Our data reveal a complex network of interactions regulating Myc destruction, and imply that enhanced protein stability contributes to oncogenic transformation by mutant Myc proteins.

Animals↗
PubMed1997

A functional role for death proteases in s-Myc- and c-Myc-mediated apoptosis.

Upon activation, cell surface death receptors, Fas/APO-1/CD95 and tumor necrosis factor receptor-1 (TNFR-1), are attached to cytosolic adaptor proteins, which in turn recruit caspase-8 (MACH/FLICE/Mch5) to activate the interleukin-1 beta-converting enzyme (ICE)/CED-3 family protease (caspase) cascade. However, it remains unknown whether these apoptotic proteases are generally involved in apoptosis triggered by other stimuli such as Myc and p53. In this study, we provide lines of evidence that a death protease cascade consisting of caspases and serine proteases plays an essential role in Myc-mediated apoptosis. When Rat-1 fibroblasts stably expressing either s-Myc or c-Myc were induced to undergo apoptosis by serum deprivation, a caspase-3 (CPP32)-like protease activity that cleaves a specific peptide substrate, Ac-DEVD-MCA, appeared in the cell lysates. Induction of s-Myc- and c-Myc-mediated apoptotic cell death was effectively prevented by caspase inhibitors such as Z-Asp-CH2-DCB and Ac-DEVD-CHO. Furthermore, exposing the cells to a serine protease inhibitor, 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), also significantly inhibited s-Myc- and c-Myc-mediated apoptosis and the appearance of the caspase-3-like protease activity in vivo. However, AEBSF did not directly inhibit caspase-3-like protease activity in the apoptotic cell lysates in vitro. Together, these results indicate that caspase-3-like proteases play a critical role in both s-Myc- and c-Myc-mediated apoptosis and that caspase-3-like proteases function downstream of the AEBSF-sensitive step in the signaling pathway of Myc-mediated apoptosis.

Animals↗
PubMed1997

Alterations in exon 1 of c-myc and expression of p62c-myc in cervical squamous cell carcinoma.

AIMS: To examine human papillomavirus (HPV) positive and negative squamous cell carcinomas of the cervix for structural alterations in exon 1 c-myc; and to investigate the expression pattern of p62, the protein product of c-myc. MATERIAL: Archival paraffin wax embedded tissues of cervical squamous cell carcinomas, stage I and II, retrieved from the files of the department of pathology, University College Cork, Ireland: 40 cases were examined for alterations in exon 1 of c-myc; 57 cases were used for immunocytochemical p62 analysis. METHODS: c-myc exon 1 PCR on HPV positive and negative stage I and II cervical squamous cell carcinomas was performed using primers designed to fragile sites in exon 1 of the c-myc oncogene, which are frequently involved in translocation phenomena and deletions in other neoplasms. This region is bordered by two promoter sequences P1 and P2. In addition, the expression of p62 was evaluated using the monoclonal antibody Mycl-9E10. RESULTS: Alterations in exon 1 of c-myc were shown in 7.5% of squamous cell carcinomas of the cervix. Changes in exon 1 and 2 of c-myc were also found in COLO 320 cells and Raji cells. These alterations were due to small deletions within exon 1 of c-myc, but point polymorphisms occurring within the priming sites (in one case) may also have occurred. The alterations uncovered appeared "clonal," as replicate samples showed the same amplicon band pattern. Expression of c-myc was variable, with cytoplasmic staining patterns predominating. All cases which showed exon 1 alterations were HPV positive and had strong nuclear positivity on p62 immunocytochemistry. CONCLUSIONS: Alterations in exon 1 of c-myc occur in a minority of cervical cancers and there was increased expression of p62 in a cohort of HPV positive and negative cervical squamous cell carcinomas. Exon 1 alterations may provide an alternative route to c-myc activation in early squamous cell carcinoma.

Carcinoma, Squamous Cell↗
PubMed1989

The human L-myc gene is expressed as two forms of protein in small cell lung carcinoma cell lines: detection by monoclonal antibodies specific to two myc homology box sequences.

The L-myc gene is the third member of the myc family of proto-oncogenes. Amplification and elevated expression of the L-myc gene has been detected in a subset of small cell lung carcinoma (SCLC) cell lines. The biological properties and functions of the L-myc gene and its product have not yet been elucidated. Monoclonal antibodies against two myc homology boxes were used to characterize the L-myc gene product. These antibodies react with two groups of polypeptides of apparent masses of 60, 61 and 66 kd (the long forms), and 34 and 37 kd (the short forms) in SCLC cells expressing L-myc transcripts. The long form L-myc proteins are associated with the nuclear fraction of the cells. The short form L-myc proteins are present in the cytoplasmic fraction, though diffusion of the short forms from the nucleus during cell fractionation cannot be ruled out. The half-life of the long form polypeptides is approximately 45-90 min. The short form polypeptides have a half-life of approximately 120-180 min. The L-myc protein is not detectable in the mitotic cells, suggesting that the L-myc protein expression is tightly regulated during the cell cycle.

Amino Acid Sequence↗
PubMed1995

Coexpression pattern of c-myc associated genes in a small cell lung cancer cell line with high steady state c-myc transcription.

The c-Myc protein is involved in cellular transformation and mitogenesis, but also works as a potent inducer of differentiation and programmed cell death. Max as an obligate heterodimeric partner for Myc mediates its functions as a specific transcriptional activator and a transforming protein. Mad and Mxi1 proteins both heterodimerize with Max and compete with each other for limiting amounts of Max. Transcriptional activation by Myc can be suppressed by increasing the amount of Mad or Mxi1. This report shows the expression pattern of these Myc related factors at the mRNA level in a small cell lung cancer (SCLC) cell line (GLC4) which is characterized by c-myc amplification and strong constitutive c-myc overexpression. We found these genes transcriptionally active but uninfluenced from high c-myc transcription. Max was constantly transcribed at a relatively low level during cell cycle progression. Mad and mxi1 mRNA was at a surprisingly high level in proliferating cells. Mad was further upregulated and mxi1 was downregulated to basal levels during serum starvation of the cells. We further analyzed the activity of c-fos, c-jun, c-myb and nm23 which are described to be involved in c-myc transcriptional activation, c-jun and c-fos were not constitutively activated and can be excluded as regulators. High steady state c-myc in contrast influences the serum stimulated transient activation mechanism of these two genes. We identified high copy number nm23 mRNA whose role as a putative c-myc transcriptional activator is under investigation. Our results indicate that constitutive overexpression of c-myc does not require the activity of the nuclear oncogenes tested and that the m-RNA expression pattern of functionally related proteins is not influenced.

Base Sequence↗
PubMed1992

An exceptional mouse plasmacytoma with a new kappa/N-myc [T(6; 12) (C1; B)] translocation expresses N-myc but not c-myc.

Mouse plasmacytomas (MPC) carry one of three reciprocal translocations that juxtapose c-myc to one of the three immunoglobulin (Ig) loci. Here we describe an exceptional MPC, induced by pristane oil and Abelson (A-MuLV) virus. It does not carry any of the three c-myc/Ig translocations, but contains a previously unknown reciprocal T(6;12) translocation affecting the bands known to carry the IgK (6C/1) and N-myc (12B) loci, respectively. Northern blot analysis showed high N-myc but no c-myc expression. This is consistent with the constitutive activation of N-myc by a juxtaposition of the IgK and N-myc loci. Reciprocal translocation in B-cell derived tumors are believed to involve the Ig loci by the action of some enzyme that participates in the physiological rearrangement of the Ig loci. Only transcriptionally active chromatin regions are accessible to such recombinases (Alt et al. 1987). N-myc is not expressed in B-cells, but it is transcriptionally active during the early pro- and pre-B cell stage, whereafter it and the surrounding chromatin region becomes inactive (Smith et al. 1992). It is therefore most likely that the N-myc/Kappa translocation has arisen at an early stage of B-cell differentiation. This would imply that the myc/Ig translocations do not block B-cell differentiation. They also reaffirm the functional equivalence of N- and c-myc in relation to B-cell carcinogenesis, as shown by our previous work on tumor induction in N-myc transgenic mice (Wang et al. 1992).

Animals↗
PubMed2001

Suppression of c-myc expression and c-Myc function in response to sustained DNA damage in MCF-7 breast tumor cells.

The topoisomerase II inhibitors teniposide (VM-26), doxorubicin, and amsacrine (m-AMSA), as well as ionizing radiation, induce a transient suppression of c-myc mRNA, which correlates with growth inhibition of MCF-7 breast tumor cells. To further assess the involvement of c-mvc in the DNA damage-induced signal transduction pathways of the breast tumor cell, we determined the influence of sustained DNA damage on c-myc expression, c-Myc protein levels and c-Myc function. Continuous exposure of MCF-7 breast tumor cells to VM-26 induced DNA strand breaks that were sustained for at least 9 hr. DNA strand breakage was accompanied by a decline in c-myc transcripts and c-Myc protein levels by >90% after VM-26 exposure for 24 hr. The activity of a transcriptional target of the c-Myc protein, ornithine decarboxylase, was reduced by approximately 75% within 9 hr of DNA damage, in parallel to the declines in c-myc mRNA and protein levels. Extended exposure to VM-26 resulted in an initial loss of approximately 35% of the cell population followed by the death of additional cells such that by 72 hr only 50% of the cells were viable. Although apoptosis was evident 72 hr after initiating drug exposure [based on cell cycle analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, and an assessment of cell morphology], the primary phase of cell killing, which occurred during the first 24 hr was non-apoptotic. These studies indicate that non-apoptotic pathways can also mediate cell death in the breast tumor cell and support the role of c-myc expression, c-Myc protein, and c-Myc function as elements of the DNA damage response pathway in the breast tumor cell.

Antineoplastic Agents↗
PubMed1999

New Myc-interacting proteins: a second Myc network emerges.

Despite its intensive investigation for almost two decades, c-Myc remains a fascinating and enigmatic subject. A large and compelling body of evidence indicates that c-Myc is a transcription factor with central roles in the regulation of cell proliferation, differentiation, and apoptosis, but its exact function has remained elusive. In this review we survey recent advances in the identification and analysis of c-Myc-binding proteins, which suggest insights into the transcriptional roles of c-Myc but which also extend the existing functional paradigms. The C-terminal domain (CTD) of c-Myc mediates interaction with Max and physiological recognition of DNA target sequences, events needed for all biological actions. Recently described interactions between the CTD and other cellular proteins, including YY-1, AP-2, BRCA-1, TFII-I, and Miz-1, suggest levels of regulatory complexity beyond Max in controlling DNA recognition by c-Myc. The N-terminal domain (NTD), which includes the evolutionarily conserved and functionally crucial Myc Box sequences (MB1 and MB2), contains the transcription activation domain (TAD) of c-Myc as well as regions required for transcriptional repression, cell cycle regulation, transformation, and apoptosis. In addition to interaction with the retinoblastoma family protein p107, the NTD has been shown to interact with alpha-tubulin and the novel adaptor proteins Binl, MM-1, Pam, TRRAP, and AMY-1. The structure of these proteins and their effects on c-Myc actions suggest links to the transcriptional regulatory machinery as well as to cell cycle regulation, chromatin modeling, and apoptosis. Investigations of this emerging NTD-based network may reveal how c-Myc is regulated and how it affects cell fate, as well as providing tools to distinguish the physiological roles of various Myc target genes.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Transforming ability of Gag-Myc fusion proteins correlates with Gag-Myc protein stability and transcriptional repression.

Avian retroviruses that have transduced c-myc are useful tools to study the conditions necessary for cellular transformation. FH3, one such retrovirus which encodes a Gag-Myc fusion protein, is not transforming in quail embryonic fibroblasts, but a late variant of FH3 that arose after passaging FH3-infected cells is transforming. Mutational analysis of FH3 revealed that the presence of a portion of the retroviral protease in FH3 inhibited transformation and that this inhibition was transferable to a more highly transforming retrovirus, MC29. Transforming and non-transforming FH3-derived and MC29-derived Gag-Myc proteins were used to further explore characteristics of Myc necessary for transformation. Gag-Myc proteins which were transforming were found to be the most stable in the cell. To distinguish whether transactivation and/or repression is correlated to transformation, the various Gag-Myc fusion proteins were tested for their ability to activate or repress c-Myc targets. Results indicated that a correlation exists between transforming Gag-Myc proteins and their ability to repress, whereas all Gag-Myc proteins could transactivate, regardless of their ability to transform. Taken together, these results suggest that protein stabilization of Myc and repression of target genes by Myc are important for cellular transformation.

Animals↗