Regulation of gene transcription by the oncoprotein MYC

Lüscher, Bernhard; Vervoorts, Jörg

doi:10.1016/j.gene.2011.12.027

Cited by 126 publications

(134 citation statements)

References 240 publications

Supporting

Mentioning

127

Contrasting

Order By: Relevance

“…In animal cells, the TFs p53 and c-Myc are central regulators of many key processes, including apoptosis. p53 and c-Myc represent excellent paradigms that illustrate the sophistication of transcription regulation by different post-translational modifications 28,29 . In particular, ubiquitination of these TFs provides efficient regulation of their stability, subcellular localization and activity 21,29 .…”

Section: Discussionmentioning

confidence: 99%

“…p53 and c-Myc represent excellent paradigms that illustrate the sophistication of transcription regulation by different post-translational modifications 28,29 . In particular, ubiquitination of these TFs provides efficient regulation of their stability, subcellular localization and activity 21,29 . In the case of c-Myc, a model has been proposed that suggests that Ub-mediated modulation of its transcriptional activity ensures tight control of highly active c-Myc that is potentially toxic to cells, for instance by inducing apoptosis 29 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Arabidopsis ubiquitin ligase MIEL1 mediates degradation of the transcription factor MYB30 weakening plant defence

et al. 2013

View full text Add to dashboard Cite

One of the most efficient plant resistance reactions to pathogen attack is the hypersensitive response, a form of programmed cell death at infection sites. The Arabidopsis transcription factor MYB30 is a positive regulator of hypersensitive cell death responses. Here we show that MIEL1 (MYB30-Interacting E3 Ligase1), an Arabidopsis RING-type E3 ubiquitin ligase that interacts with and ubiquitinates MYB30, leads to MYB30 proteasomal degradation and downregulation of its transcriptional activity. In non-infected plants, MIEL1 attenuates cell death and defence through degradation of MYB30. Following bacterial inoculation, repression of MIEL1 expression removes this negative regulation allowing sufficient MYB30 accumulation in the inoculated zone to trigger the hypersensitive response and restrict pathogen growth. Our work underlines the important role played by ubiquitination to control the hypersensitive response and highlights the sophisticated fine-tuning of plant responses to pathogen attack. Overall, this work emphasizes the importance of protein modification by ubiquitination during the regulation of transcriptional responses to stress in eukaryotic cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Arabidopsis ubiquitin ligase MIEL1 mediates degradation of the transcription factor MYB30 weakening plant defence

et al. 2013

View full text Add to dashboard Cite

show abstract

“…6 The transcriptional program regulated by MYC includes 10% to 15% of all human genes. The main cell functions and pathways under control of MYC are cell proliferation and growth, DNA replication, protein biosynthesis, and regulation of metabolism and energy.…”

Section: Myc As a Transcription Factormentioning

confidence: 99%

Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification

Ott

Rosenwald

Campo

2013

Blood

212

214

View full text Add to dashboard Cite

MYC is a potent oncogene initially identified as the target of the t(8;14)(q24;q32) chromosome translocation in Burkitt lymphoma. MYC gene alterations have been identified in other mature B-cell neoplasms that are usually associated with an aggressive clinical behavior. Most of these tumors originate in cells that do not normally express MYC protein. The oncogenic events leading to MYC up-regulation seem to overcome the inhibitory effect of physiological repressors such as BCL6 or BLIMP1.Aggressive lymphomas frequently carry additional oncogenic alterations that cooperate with MYC dysregulation, likely counteracting its proapoptotic function. The development of FISH probes and new reliable antibodies have facilitated the study of MYC gene alterations and protein expression in large series of patients, providing new clinical and biological perspectives regarding MYC dysregulation in aggressive lymphomas. MYC gene alterations in large B-cell lymphomas are frequently associated with BCL2 or BCL6 translocations conferring a very aggressive behavior. Conversely, MYC protein up-regulation may occur in tumors without apparent gene alterations, and its association with BCL2 overexpression also confers a poor prognosis. In this review, we integrate all of this new information and discuss perspectives, challenges, and open questions for the diagnosis and management of patients with MYC-driven aggressive B-cell lymphomas. (Blood. 2013;122(24):3884-3891) Introduction MYC was initially identified as the target oncogene dysregulated by the t(8;14)(q24;q32) translocation in Burkitt lymphoma (BL). MYC rearrangements involving the heavy-and light-chain immunoglobulin (IGL) loci and different non-IG genes were subsequently detected in other lymphoid neoplasms usually associated with very aggressive clinical behavior.1,2 The transforming oncogenic potential of MYC was initially demonstrated in cell lines and transgenic animal models. However, MYC dysregulation alone does not cause lymphoma, 4 and the t(8;14) has been found at very low levels in blood and BM of healthy individuals, 5 indicating that this genetic alteration per se is not sufficient to trigger lymphomagenesis. BL and most lymphomas carrying MYC translocations are among the most proliferative tumors. However, MYC expression has been difficult to identify in the germinal center (GC), the lymphoid cell compartment with the highest proliferative fraction, where most of these tumors originate. Understanding the possible role of MYC in normal lymphoid regulation and particularly the modulation of the GC reaction has been elusive.Recent studies, including basic immunology analyses, new animal models, next-generation sequencing, and clinicopathological observations, are converging to provide a new perspective of the role of MYC in the lymphoid system and the pathogenesis of aggressive lymphomas. In this review, we integrate all of this new information and discuss new perspectives, challenges, and open questions for the diagnosis and management of patients. MYC as a transc...

show abstract

“…Among others, such complexes include epigenetic writers, like histoneacetyltransferases (HAT), epigenetic readers, like BET proteins, or the basal transcription machinery, like the TATA box-binding protein (TBP; refs. [70][71][72]). An important role for MYC in the release of the paused RNA Pol II at the proximal promoter of MYC-bound genes was demonstrated (73).…”

Section: Targeting Myc Indirectlymentioning

confidence: 99%

Concepts to Target MYC in Pancreatic Cancer

Wirth

Mahboobi

Krämer

et al. 2016

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Current data suggest that MYC is an important signaling hub and driver in pancreatic ductal adenocarcinoma (PDAC), a tumor entity with a strikingly poor prognosis. No targeted therapies with a meaningful clinical impact were successfully developed against PDAC so far. This points to the need to establish novel concepts targeting the relevant drivers of PDAC, like KRAS or MYC. Here, we discuss recent developments of direct or indirect MYC inhibitors and their potential mode of action in PDAC.

show abstract

Regulation of gene transcription by the oncoprotein MYC

Cited by 126 publications

References 240 publications

Arabidopsis ubiquitin ligase MIEL1 mediates degradation of the transcription factor MYB30 weakening plant defence

Arabidopsis ubiquitin ligase MIEL1 mediates degradation of the transcription factor MYB30 weakening plant defence

Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification

Concepts to Target MYC in Pancreatic Cancer

Contact Info

Product

Resources

About