TRRAP-Dependent and TRRAP-Independent Transcriptional Activation by Myc Family Oncoproteins

Nikiforov, Mikhail A.; Chandriani, Sanjay; Park, Jeong-Hyeon; Kotenko, Iulia; Matheos, Dina P.; Johnsson, Anna; McMahon, Steven B.; Cole, Michael

doi:10.1128/mcb.22.14.5054-5063.2002

Cited by 123 publications

(136 citation statements)

References 51 publications

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“…29 For protein analysis, aliquots of whole-cell or nuclear lysates (50-80 mg of protein) were separated on SDS-acrylamide gels and blotted onto a Protran BA85 nitrocellulose membrane (Schleicher & Schüll). They were then incubated with antibodies specific for p53 (CM-5, Novocastra), p21 (C-19), Mdm2 (SMP14), Bax (B-9), Bcl-xl (S-18), cyclin E (M-20), E2F1 (KH-95 and C-20), c-Myc (N-262), PCNA (F-2), (all from Santa Cruz Biotechnology); Bak (65371, BD Pharmingen), Bcl2 (610538), Cdk2 (C18520), Cdk4 (C18720), p27 (K25020) (all from Transduction Laboratories); p19ARF (ab80, Novus Biologicals); MAPK (3A7; Cell Signaling), and MIF (a gift from C. Metz, North Shore Hospital, Manhasset, NY).…”

Section: Expression Analysismentioning

confidence: 99%

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MIF loss impairs Myc-induced lymphomagenesis

et al. 2005

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Macrophage migration inhibitory factor (MIF) is a potent regulator of inflammation and cell growth. Using the El-Myc lymphoma mouse model, we demonstrate that loss of MIF markedly delays the onset of B-cell lymphoma development in vivo. The molecular basis for this MIF-loss-induced phenotype is the perturbed DNA-binding activity of E2F factors and the concomitantly enhanced tumor suppressor activity of the p53 pathway. Accordingly, premalignant MIF-null El-Myc Bcells are predisposed to delayed S-phase progression and increased apoptosis. MIF-deficient lymphomas that do arise under these conditions contain frequent ARF deletions and p53 inactivating mutations. Conversely, MIF expression is retained in tumors developed by wild-type El-Myc animals, and the presence of one or both MIF alleles is sufficient to accelerate the development of Myc-induced lymphomas. Collectively, these results indicate that MIF promotes Mycmediated tumorigenesis, at least in the B-lymphoid compartment, and implicate MIF as a mediator of malignant cell growth in vivo.

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Section: Expression Analysismentioning

confidence: 99%

“…Chromatin immunoprecipitation (ChIP) assays were performed as previously described 29 with a few modifications. The cells were fixed with 1% formaldehyde for 1 h at room temperature with mild shaking.…”

Section: Chromatin Immunoprecipitation Assaysmentioning

confidence: 99%

MIF loss impairs Myc-induced lymphomagenesis

et al. 2005

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“…The MB2 sequence is unique to Myc and evolutionarily highly conserved in all Myc proteins, down to invertebrates (reviewed in Gallant, 2006). Elimination of MB2 blocks or severely impairs all of Myc's biological activities that have been tested in cultured cells: the ability to promote cellular proliferation (Lee et al, 1997;Conzen et al, 2000;Hirst and Grandori, 2000;Kenney et al, 2003), apoptosis (Evan et al, 1992;Conzen et al, 2000;Dugan et al, 2002;Oster et al, 2003;, transformation (Sarid et al, 1987;Stone et al, 1987;Li et al, 1994;Brough et al, 1995;McMahon et al, 1998;Conzen et al, 2000;McMahon et al, 2000;Nikiforov et al, 2002;Oster et al, 2003;, and block differentiation (Freytag et al, 1990).…”

Section: To Molecularly Understand How Myc Controls Its Target Genes mentioning

confidence: 99%

“…Furthermore, an MB2-mutant Myc very inefficiently rescues the proliferation defect of rat fibroblasts lacking endogenous c-Myc (Bush et al, 1998;Xiao et al, 1998;Nikiforov et al, 2002;Oster et al, 2003). The MB2 motif is required for the efficient interaction with several co-factors such as TRRAP and associated HATs (McMahon et al, 1998;Bouchard et al, 2001;Frank et al, 2001;Nikiforov et al, 2002), the HAT complex component BAF53 , TIP48 & TIP49 , Skp2 (Kim et al, 2003;von der Lehr et al, 2003), and for the stimulation of pre-mRNA capping (Cowling and Cole, 2007).…”

Section: To Molecularly Understand How Myc Controls Its Target Genes mentioning

confidence: 99%

“…The MB2 motif is required for the efficient interaction with several co-factors such as TRRAP and associated HATs (McMahon et al, 1998;Bouchard et al, 2001;Frank et al, 2001;Nikiforov et al, 2002), the HAT complex component BAF53 , TIP48 & TIP49 , Skp2 (Kim et al, 2003;von der Lehr et al, 2003), and for the stimulation of pre-mRNA capping (Cowling and Cole, 2007). Nevertheless, it has been shown that a Myc mutant lacking MB2 still efficiently activates the expression of some target genes and artificial reporters (Kato et al, 1990;BelloFernandez et al, 1993;Li et al, 1994;Brough et al, 1995;Lee et al, 1997;Xiao et al, 1998;Nikiforov et al, 2002), although many targets are only poorly activated by such a protein (Conzen et al, 2000;Hirst and Grandori, 2000;Bouchard et al, 2001;Nikiforov et al, 2002;Kenney et al, 2003;Cowling and Cole, 2007). Such a MycΔMB2 mutant also fails to repress the genes that are normally down-regulated by wild type Myc (Li et al, 1994;Lee et al, 1997), including the c-myc locus itself (Penn et al, 1990;Bush et al, 1998;Oster et al, 2003).…”

Section: To Molecularly Understand How Myc Controls Its Target Genes mentioning

confidence: 99%

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The conserved Myc box 2 and Myc box 3 regions are important, but not essential, for Myc function in vivo

Schwinkendorf¹,

Gallant²

2009

Gene

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Regulation and Function of the MYC Oncogene

Kalkat

Penn

2013

Encyclopedia of Life Sciences

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The MYC oncogene has been the subject of intense study for more than 30 years, due to its important role in tumourigenesis. MYC is a nuclear transcription factor that can regulate the expression of a multitude of target genes, and its expression in tumours is often associated with poor prognosis. Although decades of research have provided insights into its molecular function as a transcription factor, the mechanisms by which MYC can induce cellular transformation have remained elusive. In addition to the regulation of genes important for cell cycle progression, metabolism, apoptosis and angiogenesis, MYC has wide‐reaching effects, including the alteration of cellular epigenetics and total ribonucleic acid (RNA) content. Recent reports have suggested that post‐translational modification (PTM) of MYC is important for regulating the activity and functions of this potent oncogene; however, surprisingly, little research has been conducted in this area. Herein, the authors summarise recent findings regarding the molecular and biological functions of MYC and their relationship to the PTMs of MYC. Key Concepts: The MYC oncogene encodes a nuclear basic helix‐loop‐helix transcription factor. MYC regulates a large number of transcriptional targets and can have wide‐reaching effects on proliferation, the epigenome and total cellular RNA content. MYC is essential for cellular proliferation and is a potent oncogene when it is deregulated in cancer. Deregulated, often elevated, MYC levels have been shown to initiate tumourigenesis in many in vivo models. MYC activity and stability is regulated by post‐translational modifications, including phosphorylation, ubiquitylation and acetylation.

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TRRAP-Dependent and TRRAP-Independent Transcriptional Activation by Myc Family Oncoproteins

Cited by 123 publications

References 51 publications

MIF loss impairs Myc-induced lymphomagenesis

MIF loss impairs Myc-induced lymphomagenesis

The conserved Myc box 2 and Myc box 3 regions are important, but not essential, for Myc function in vivo

Regulation and Function of the MYC Oncogene

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