The Oscar-worthy role of Myc in apoptosis

Meyer, Natalie; Kim, Sam S.; Penn, Linda Z.

doi:10.1016/j.semcancer.2006.07.011

Cited by 115 publications

(97 citation statements)

References 165 publications

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“…Inactivating mutations in TP53 are also common in BL, occurring in 35% of cases. The selection for these mutations is likely to stem from the fact that overexpression of MYC in primary cells induces TP53-dependent apoptotic pathways (Evan et al 1992;Meyer et al 2006). …”

Section: Genetics Of Blmentioning

confidence: 99%

Oncogenic Mechanisms in Burkitt Lymphoma

Schmitz

Ceribelli

Pittaluga

et al. 2014

Cold Spring Harbor Perspectives in Medicine

204

174

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Burkitt lymphoma is a germinal center B-cell-derived cancer that was instrumental in the identification of MYC as an important human oncogene more than three decades ago. Recently, new genomics technologies have uncovered several additional oncogenic mechanisms that cooperate with MYC to create this highly aggressive cancer. The transcription factor TCF-3 is central to Burkitt lymphoma pathogenesis. TCF-3 is rendered constitutively active in Burkitt lymphoma by two related mechanisms: (1) somatic mutations that inactivate its negative regulator ID3, and (2) somatic mutations in TCF-3 that block the ability of ID3 to bind and interfere with its activity as a transcription factor. TCF-3 is also a master regulator of normal germinal center B-cell differentiation. Within the germinal center, TCF-3 up-regulates genes that are characteristically expressed in the rapidly dividing centroblasts, the putative cell of origin for Burkitt lymphoma, while repressing genes expressed in the less proliferative centrocytes. TCF-3 promotes antigen-independent (tonic) B-cell-receptor signaling in Burkitt lymphoma by transactivating immunoglobulin heavy-and light-chain genes while repressing PTPN6, which encodes the phosphatase SHP-1, a negative regulator of Bcell-receptor signaling. Tonic B-cell-receptor signaling sustains Burkitt lymphoma survival by engaging the PI3 kinase pathway. In addition, TCF-3 promotes cell-cycle progression by transactivating CCND3, encoding a D-type cyclin that regulates the G 1 -S phase transition. Additionally, CCND3 accumulates oncogenic mutations that stabilize cyclin D3 protein expression and drive proliferation. These new insights into Burkitt lymphoma pathogenesis suggest new therapeutic strategies, which are sorely needed in developing regions of the world where this cancer is endemic.

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Section: Genetics Of Blmentioning

confidence: 99%

Oncogenic Mechanisms in Burkitt Lymphoma

Schmitz

Ceribelli

Pittaluga

et al. 2014

Cold Spring Harbor Perspectives in Medicine

204

174

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“…MYC is generally recognized as an important regulator of proliferation, growth, differentiation and apoptosis [29,30] . Therefore, it is also accepted that the deregulation of MYC expression is a major event in cancer pathogenesis or progression.…”

Section: Myc and Cancermentioning

confidence: 99%

MYC and gastric adenocarcinoma carcinogenesis

Calcagno¹,

Leal²,

Assumpção³

et al. 2008

WJG

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MYC is an oncogene involved in cell cycle regulation, cell growth arrest, cell adhesion, metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function. It has been described as a key element of several carcinogenesis processes in humans. Many studies have shown an association between MYC deregulation and gastric cancer. MYC deregulation is also seen in gastric preneoplastic lesions and thus it may have a role in early gastric carcinogenesis. Several studies have suggested that amplification is the main mechanism of MYC deregulation in gastric cancer.In the present review, we focus on the deregulation of the MYC oncogene in gastric adenocarcinoma c a r c i n o g e n e s i s , i n c l u d i n g i t s a s s o c i a t i o n w i t h Helicobacter pylori (H pylori ) MYC AND CANCERMYC gene was found to be the cellular homolog of retroviral v-myc oncogene about 30 years ago [12][13][14] . It is located on chromosomal region 8q24.1, has 3 exons [15,16] and encodes a nuclear phosphoprotein [17] . MYC has to heteromerize with MAX, a protein expressed constitutively, to acquire DNA-binding activity. MYC/MAX dimmers are made viable by a basic region helix-loop-helix leucine-zipper motif (bHLHZip), conserved sequences in the carboxyl terminus of both proteins. MYC/MAX dimmers bind to E-box sequence CACGTG in the promoters of specific target genes and stimulate their transcription [18] . MYC has an effect on up to about 15% of genes in genomes of many organisms, from flies to humans [19] . Groups of genes involved in cell cycle regulation, metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function are over-represented in the Myc target gene network.MYC also consistently represses genes involved in cell growth arrest and cell adhesion [20] . Dominguez-Sola et al [21] recently showed that Myc interacts with the prereplicative complex and localizes to early sites of DNA synthesis. Thus, it also has a direct role in the control of DNA replication.MYC regulates transcription from its targets through several mechanisms, including recruitment of histone acetylases, chromatin modulating proteins, basal transcription factors and DNA methyltransferase [22][23][24][25][26] . Protein products of MYC target genes g o on to mediate the downstream effects of MYC on cell biology. MYC is then rapidly degraded, and the pathway switches to a transcriptionally repressive state when MAX dimerizes with a group of related bHLH-Zip proteins, the MAD family, that act as MYC antagonists [27] ( Figure 1).MYC expression might be regulated transcriptionally (initiation and elongation), post-transcriptionally (mRNA stability and translation) or post-translationally (protein stability) [28] . MYC is generally recognized as an important regulator of proliferation, growth, differentiation and apoptosis [29,30] . Therefore, it is also accepted that the deregulation of MYC expression is a major event in cancer pathogenesis or progression. Deregulated expression of a wild-type MYC protein is suff...

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“…The 8q24.21 susceptibility region has been described as a gene-desert because of the lacking of annotated protein-coding genes [19]. However, the c-MYC oncogene, which is located 300 kb telomeric, seems the most likely candidate to be functionally linked to the susceptibility conferred by the 8q24.21 SNPs and there is evidence that its expression may be affected by SNPs within 8q24.21 region [17,20].…”

Section: Introductionmentioning

confidence: 99%