IndraLab

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MYC increases the amount of CDKN2A. 10 / 13
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"For example, while Myc binds to E-boxes of the p16 promoter and up-regulates p16 transcription, it has also been demonstrated that Myc can activate Bmi1, a potent repressor of the entire INK4b/ARF/INK4a locus."
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"These findings imply that let-7g might function as an inhibitor of HCC cell proliferation through direct repression of c-Myc, which may lead to re-expression of the tumor suppressor p16INK4A [XREF_BIBR]."
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"We have shown that the cyclin dependent kinase Cdk2, although redundant for cell cycle progression, has a unique role in suppressing a Myc induced senescence program : Myc activation elicited expression of p16 (INK4a) and p21 (Cip1), and caused senescence in cells lacking Cdk2, but not in Cdk2-proficient cells."
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"studies showing that the ARF gene encoded by the tumor-suppressive gene locus, INK4A, is induced after expression of c-MYC or other mitogenic transcription factors, like E2F [33]. The authors suggest that activation of cell cycle deregulating genes is translated into activation of the ARF gene, which encodes a p53-stabilizing protein [34]. Consistent with this model, fibroblasts from ARF-/- mice are largely refractory to c-MYC-induced apoptosis"
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"XREF_BIBR, XREF_BIBR, XREF_BIBR Furthermore, c-MYC has been reported to directly induce the expression of p19 and ARF, which also belongs to the INK4 locus."
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"For example, physiologic thresholds of Myc and Ras signaling do not activate Arf gene expression, but overexpression of Myc and oncogenic Ras induces Arf."
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"In these cell types, Myc induces the expression of p19 Arf, which, by inactivating Mdm2, helps to enhance p53 dependent apoptosis (Zindy et al., 1998)."
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"Oncogenic c-Myc can indirectly induce the expression of the tumor suppressor ARF, which leads to apoptosis through the stabilization of p53, but both c-Myc and ARF have apoptotic activities that are independent of p53."
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"In addition, both c-Myc and E2F-1 induce Arf expression."
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"For example, MYC induces the expression of the tumor suppressor ARF."
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