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c-Myc antibody [Y69]

RRID:AB_731658

Antibody ID

AB_731658

Target Antigen

c-Myc antibody [Y69] human, mouse, rat

Proper Citation

(Abcam Cat# ab32072, RRID:AB_731658)

Clonality

monoclonal antibody

Comments

validation status unknown, seller recommendations provided in 2012: Western Blot; Immunohistochemistry; Immunofluorescence; Immunocytochemistry; Immunohistochemistry - fixed; Immunoprecipitation; ICC/IF, IHC-P, IP, WB

Host Organism

rabbit

Vendor

Abcam

The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma.

  • McBride MJ
  • Cancer Cell
  • 2018 Jun 11

Literature context:


Abstract:

Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 subunit assembly. Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate an SS transcriptional signature that we define using primary tumors and cell lines. Specifically, SS18-SSX retargets BAF complexes from enhancers to broad polycomb domains to oppose PRC2-mediated repression and activate bivalent genes. Upon suppression of SS18-SSX, reassembly of BAF47 restores enhancer activation, but is not required for proliferative arrest. These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations.

Funding information:
  • NIAID NIH HHS - R01 AI076479(United States)

The GSK3 Signaling Axis Regulates Adaptive Glutamine Metabolism in Lung Squamous Cell Carcinoma.

  • Momcilovic M
  • Cancer Cell
  • 2018 May 14

Literature context:


Abstract:

Altered metabolism is a hallmark of cancer growth, forming the conceptual basis for development of metabolic therapies as cancer treatments. We performed in vivo metabolic profiling and molecular analysis of lung squamous cell carcinoma (SCC) to identify metabolic nodes for therapeutic targeting. Lung SCCs adapt to chronic mTOR inhibition and suppression of glycolysis through the GSK3α/β signaling pathway, which upregulates glutaminolysis. Phospho-GSK3α/β protein levels are predictive of response to single-therapy mTOR inhibition while combinatorial treatment with the glutaminase inhibitor CB-839 effectively overcomes therapy resistance. In addition, we identified a conserved metabolic signature in a broad spectrum of hypermetabolic human tumors that may be predictive of patient outcome and response to combined metabolic therapies targeting mTOR and glutaminase.

Funding information:
  • NIAMS NIH HHS - R01 AR061567(United States)

R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m6A/MYC/CEBPA Signaling.

  • Su R
  • Cell
  • 2018 Jan 11

Literature context:


Abstract:

R-2-hydroxyglutarate (R-2HG), produced at high levels by mutant isocitrate dehydrogenase 1/2 (IDH1/2) enzymes, was reported as an oncometabolite. We show here that R-2HG also exerts a broad anti-leukemic activity in vitro and in vivo by inhibiting leukemia cell proliferation/viability and by promoting cell-cycle arrest and apoptosis. Mechanistically, R-2HG inhibits fat mass and obesity-associated protein (FTO) activity, thereby increasing global N6-methyladenosine (m6A) RNA modification in R-2HG-sensitive leukemia cells, which in turn decreases the stability of MYC/CEBPA transcripts, leading to the suppression of relevant pathways. Ectopically expressed mutant IDH1 and S-2HG recapitulate the effects of R-2HG. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. Collectively, while R-2HG accumulated in IDH1/2 mutant cancers contributes to cancer initiation, our work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m6A/MYC/CEBPA signaling.

Funding information:
  • NCI NIH HHS - R01 CA178454()
  • NCI NIH HHS - R01 CA182528()
  • NCI NIH HHS - R01 CA211614()
  • NCI NIH HHS - R01 CA214965()
  • NCI NIH HHS - R50 CA211404()
  • NHGRI NIH HHS - RM1 HG008935()
  • NIGMS NIH HHS - NIH R01 GM087650(United States)
  • NIGMS NIH HHS - R01 GM071440()
  • NINDS NIH HHS - R01 NS089815()
  • NINDS NIH HHS - R21 NS100077()

Replication Study: Transcriptional amplification in tumor cells with elevated c-Myc.

  • Lewis LM
  • Elife
  • 2018 Jan 9

Literature context:


Abstract:

As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Blum et al., 2015), that described how we intended to replicate selected experiments from the paper 'Transcriptional amplification in tumor cells with elevated c-Myc' (Lin et al., 2012). Here we report the results. We found overexpression of c-Myc increased total levels of RNA in P493-6 Burkitt's lymphoma cells; however, while the effect was in the same direction as the original study (Figure 3E; Lin et al., 2012), statistical significance and the size of the effect varied between the original study and the two different lots of serum tested in this replication. Digital gene expression analysis for a set of genes was also performed on P493-6 cells before and after c-Myc overexpression. Transcripts from genes that were active before c-Myc induction increased in expression following c-Myc overexpression, similar to the original study (Figure 3F; Lin et al., 2012). Transcripts from genes that were silent before c-Myc induction also increased in expression following c-Myc overexpression, while the original study concluded elevated c-Myc had no effect on silent genes (Figure 3F; Lin et al., 2012). Treating the data as paired, we found a statistically significant increase in gene expression for both active and silent genes upon c-Myc induction, with the change in gene expression greater for active genes compared to silent genes. Finally, we report meta-analyses for each result.

Funding information:
  • NHLBI NIH HHS - U01HL098179(United States)

Mutant p53 Gains Its Function via c-Myc Activation upon CDK4 Phosphorylation at Serine 249 and Consequent PIN1 Binding.

  • Liao P
  • Mol. Cell
  • 2017 Dec 21

Literature context:


Abstract:

TP53 missense mutations significantly influence the development and progression of various human cancers via their gain of new functions (GOF) through different mechanisms. Here we report a unique mechanism underlying the GOF of p53-R249S (p53-RS), a p53 mutant frequently detected in human hepatocellular carcinoma (HCC) that is highly related to hepatitis B infection and aflatoxin B1. A CDK inhibitor blocks p53-RS's nuclear translocation in HCC, whereas CDK4 interacts with p53-RS in the G1/S phase of the cells, phosphorylates it, and enhances its nuclear localization. This is coupled with binding of a peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) to p53-RS, but not the p53 form with mutations of four serines/threonines previously shown to be crucial for PIN1 binding. As a result, p53-RS interacts with c-Myc and enhances c-Myc-dependent rDNA transcription key for ribosomal biogenesis. These results unveil a CDK4-PIN1-p53-RS-c-Myc pathway as a novel mechanism for the GOF of p53-RS in HCC.

Funding information:
  • NHLBI NIH HHS - R00HL-091133(United States)

Global Inhibition with Specific Activation: How p53 and MYC Redistribute the Transcriptome in the DNA Double-Strand Break Response.

  • Porter JR
  • Mol. Cell
  • 2017 Sep 21

Literature context:


Abstract:

In response to stresses, cells often halt normal cellular processes, yet stress-specific pathways must bypass such inhibition to generate effective responses. We investigated how cells redistribute global transcriptional activity in response to DNA damage. We show that an oscillatory increase of p53 levels in response to double-strand breaks drives a counter-oscillatory decrease of MYC levels. Using RNA sequencing (RNA-seq) of newly synthesized transcripts, we found that p53-mediated reduction of MYC suppressed general transcription, with the most highly expressed transcripts reduced to a greater extent. In contrast, upregulation of p53 targets was relatively unaffected by MYC suppression. Reducing MYC during the DNA damage response was important for cell-fate regulation, as counteracting MYC repression reduced cell-cycle arrest and elevated apoptosis. Our study shows that global inhibition with specific activation of transcriptional pathways is important for the proper response to DNA damage; this mechanism may be a general principle used in many stress responses.

Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Receptor Signaling in Cancer.

  • Nabet BY
  • Cell
  • 2017 Jul 13

Literature context:


Abstract:

Interactions between stromal fibroblasts and cancer cells generate signals for cancer progression, therapy resistance, and inflammatory responses. Although endogenous RNAs acting as damage-associated molecular patterns (DAMPs) for pattern recognition receptors (PRRs) may represent one such signal, these RNAs must remain unrecognized under non-pathological conditions. We show that triggering of stromal NOTCH-MYC by breast cancer cells results in a POL3-driven increase in RN7SL1, an endogenous RNA normally shielded by RNA binding proteins SRP9/14. This increase in RN7SL1 alters its stoichiometry with SRP9/14 and generates unshielded RN7SL1 in stromal exosomes. After exosome transfer to immune cells, unshielded RN7SL1 drives an inflammatory response. Upon transfer to breast cancer cells, unshielded RN7SL1 activates the PRR RIG-I to enhance tumor growth, metastasis, and therapy resistance. Corroborated by evidence from patient tumors and blood, these results demonstrate that regulation of RNA unshielding couples stromal activation with deployment of RNA DAMPs that promote aggressive features of cancer. VIDEO ABSTRACT.

Stabilization of the c-Myc Protein by CAMKIIγ Promotes T Cell Lymphoma.

  • Gu Y
  • Cancer Cell
  • 2017 Jul 10

Literature context:


Abstract:

Although high c-Myc protein expression is observed alongside MYC amplification in some cancers, in most cases protein overexpression occurs in the absence of gene amplification, e.g., T cell lymphoma (TCL). Here, Ca2+/calmodulin-dependent protein kinase II γ (CAMKIIγ) was shown to stabilize the c-Myc protein by directly phosphorylating it at serine 62 (S62). Furthermore, CAMKIIγ was shown to be essential for tumor maintenance. Inhibition of CAMKIIγ with a specific inhibitor destabilized c-Myc and reduced tumor burden. Importantly, high CAMKIIγ levels in patient TCL specimens correlate with increased c-Myc and pS62-c-Myc levels. Together, the CAMKIIγ:c-Myc axis critically influences the development and maintenance of TCL and represents a potential therapeutic target for TCL.

Oncogenic Activation of the RNA Binding Protein NELFE and MYC Signaling in Hepatocellular Carcinoma.

  • Dang H
  • Cancer Cell
  • 2017 Jul 10

Literature context:


Abstract:

Global transcriptomic imbalance is a ubiquitous feature associated with cancer, including hepatocellular carcinoma (HCC). Analyses of 1,225 clinical HCC samples revealed that a large numbers of RNA binding proteins (RBPs) are dysregulated and that RBP dysregulation is associated with poor prognosis. We further identified that oncogenic activation of a top candidate RBP, negative elongation factor E (NELFE), via somatic copy-number alterations enhanced MYC signaling and promoted HCC progression. Interestingly, NELFE induces a unique tumor transcriptome by selectively regulating MYC-associated genes. Thus, our results revealed NELFE as an oncogenic protein that may contribute to transcriptome imbalance in HCC through the regulation of MYC signaling.

Funding information:
  • Intramural NIH HHS - Z01 BC010876-01()
  • Intramural NIH HHS - ZIA BC010877-09()
  • NCI NIH HHS - Z01 BC010876()
  • NCI NIH HHS - Z01 BC010877()
  • NHLBI NIH HHS - P01 HL131471()

Kupffer Cell-Derived Tnf Triggers Cholangiocellular Tumorigenesis through JNK due to Chronic Mitochondrial Dysfunction and ROS.

  • Yuan D
  • Cancer Cell
  • 2017 Jun 12

Literature context:


Abstract:

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant, heterogeneous cancer with poor treatment options. We found that mitochondrial dysfunction and oxidative stress trigger a niche favoring cholangiocellular overgrowth and tumorigenesis. Liver damage, reactive oxygen species (ROS) and paracrine tumor necrosis factor (Tnf) from Kupffer cells caused JNK-mediated cholangiocellular proliferation and oncogenic transformation. Anti-oxidant treatment, Kupffer cell depletion, Tnfr1 deletion, or JNK inhibition reduced cholangiocellular pre-neoplastic lesions. Liver-specific JNK1/2 deletion led to tumor reduction and enhanced survival in Akt/Notch- or p53/Kras-induced ICC models. In human ICC, high Tnf expression near ICC lesions, cholangiocellular JNK-phosphorylation, and ROS accumulation in surrounding hepatocytes are present. Thus, Kupffer cell-derived Tnf favors cholangiocellular proliferation/differentiation and carcinogenesis. Targeting the ROS/Tnf/JNK axis may provide opportunities for ICC therapy.

Funding information:
  • NIDDK NIH HHS - R01 DK107220()

In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming.

  • Ocampo A
  • Cell
  • 2016 Dec 15

Literature context:


Abstract:

Aging is the major risk factor for many human diseases. In vitro studies have demonstrated that cellular reprogramming to pluripotency reverses cellular age, but alteration of the aging process through reprogramming has not been directly demonstrated in vivo. Here, we report that partial reprogramming by short-term cyclic expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) ameliorates cellular and physiological hallmarks of aging and prolongs lifespan in a mouse model of premature aging. Similarly, expression of OSKM in vivo improves recovery from metabolic disease and muscle injury in older wild-type mice. The amelioration of age-associated phenotypes by epigenetic remodeling during cellular reprogramming highlights the role of epigenetic dysregulation as a driver of mammalian aging. Establishing in vivo platforms to modulate age-associated epigenetic marks may provide further insights into the biology of aging.

The prostate cancer TMPRSS2:ERG fusion synergizes with the vitamin D receptor (VDR) to induce CYP24A1 expression-limiting VDR signaling.

  • Kim JS
  • Endocrinology
  • 2014 Sep 25

Literature context:


Abstract:

A number of preclinical studies have shown that the activation of the vitamin D receptor (VDR) reduces prostate cancer (PCa) cell and tumor growth. The majority of human PCas express a transmembrane protease serine 2 (TMPRSS2):erythroblast transformation-specific (ETS) fusion gene, but most preclinical studies have been performed in PCa models lacking TMPRSS2:ETS in part due to the limited availability of model systems expressing endogenous TMPRSS2:ETS. The level of the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D), is controlled in part by VDR-dependent induction of cytochrome P450, family 24, subfamily 1, polypeptide1 (CYP24A1), which metabolizes 1,25D to an inactive form. Because ETS factors can cooperate with VDR to induce rat CYP24A1, we tested whether TMPRSS2:ETS would cause aberrant induction of human CYP24A1 limiting the activity of VDR. In TMPRSS2:ETS positive VCaP cells, depletion of TMPRSS2:ETS substantially reduced 1,25D-mediated CYP24A1 induction. Artificial expression of the type VI+72 TMPRSS2:ETS isoform in LNCaP cells synergized with 1,25D to greatly increase CYP24A1 expression. Thus, one of the early effects of TMPRSS2:ETS in prostate cells is likely a reduction in intracellular 1,25D, which may lead to increased proliferation. Next, we tested the net effect of VDR action in TMPRSS2:ETS containing PCa tumors in vivo. Unlike previous animal studies performed on PCa tumors lacking TMPRSS2:ETS, EB1089 (seocalcitol) (a less calcemic analog of 1,25D) did not inhibit the growth of TMPRSS2:ETS containing VCaP tumors in vivo, suggesting that the presence of TMPRSS2:ETS may limit the growth inhibitory actions of VDR. Our findings suggest that patients with TMPRSS2:ETS negative tumors may be more responsive to VDR-mediated growth inhibition and that TMPRSS2:ETS status should be considered in future clinical trials.

Funding information:
  • NIMH NIH HHS - R01-MH096705(United States)