Pim kinase-dependent inhibition of c-Myc degradation

Zhang, Yandong; Wang, Z; Li, X; Magnuson, Nancy S.

doi:10.1038/onc.2008.123

Cited by 219 publications

(237 citation statements)

References 32 publications

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“…The knockdown efficiency correlated with the strength of the inhibitory effect on cell proliferation ('gene dose effect,' see Figures 3, 4 and 7). Thus, these results confirm previous studies, which had shown that the reduction of endogenous Pim-1 levels by RNAi negatively affects the proliferation capacity of the human lung carcinoma cell line H1299, of the prostate cancer cell line PC-3 and of K562 cells (Zhang et al, 2007(Zhang et al, , 2008(Zhang et al, , 2010.…”

Section: Discussionsupporting

confidence: 81%

“…miR-33a and cancer M Thomas et al miR-33a may negatively affect cell proliferation through reduction of Pim-1, since a previous study (Zhang et al, 2008) had suggested a direct role of Pim-1 in regulating K562 cell proliferation. Indeed, under reduced serum conditions (2% fetal calf serum (FCS)), but not in the presence of 10% FCS (Supplementary Figure S3a), an anti-proliferative effect of the miR-33a mimic was observed in K562 cells (Figure 7a).…”

Section: A Mir-33a Mimic Decelerates Tumor Cell Proliferationmentioning

confidence: 99%

“…So-called survival kinases such as Akt, which promote anti-apoptotic responses or execute crucial steps in cell cycle progression, have received attention as therapeutic targets (Crowell et al, 2007;Martelli et al, 2007). This is also true for the Pim-1 kinase that can function in a synergistic manner with cMyc to establish severe forms of B-cell lymphomas (van Lohuizen et al, 1989;Verbeek et al, 1991;Zippo et al, 2007;Zhang et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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The proto-oncogene Pim-1 is a target of miR-33a

et al. 2011

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The constitutively active serine/threonine kinase Pim-1 is upregulated in different cancer types, mainly based on the action of several interleukines and growth factors at the transcriptional level. So far, a regulation of oncogenic Pim-1 by microRNAs (miRNAs) has not been reported. Here, we newly establish miR-33a as a miRNA with potential tumor suppressor activity, acting through inhibition of Pim-1. A screen for miRNA expression in K562 lymphoma, LS174T colon carcinoma and several other cell lines revealed generally low endogenous miR33a levels relative to other miRNAs. Transfection of K562 and LS174T cells with a miR-33a mimic reduced Pim-1 levels substantially. In contrast, the cell-cycle regulator cyclin-dependent kinase 6 predicted to be a conserved miR-33a target, was not downregulated by the miR-33a mimic. Seed mutagenesis of the Pim-1 3 0 -untranslated region in a luciferase reporter construct and in a Pim-1 cDNA expressed in Pim-1-deficient Skov-3 cells demonstrated specific and direct downregulation of Pim-1 by the miR-33a mimic. The persistence of this effect was comparable to that of a small interfering RNA-mediated knockdown of Pim-1, resulting in decelerated cell proliferation. In conclusion, we demonstrate the potential of miR-33a to act as a tumor suppressor miRNA, which suggests miR-33a replacement therapy through delivery of miR mimics as a novel therapeutic strategy.

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Section: Discussionsupporting

confidence: 81%

Section: A Mir-33a Mimic Decelerates Tumor Cell Proliferationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The proto-oncogene Pim-1 is a target of miR-33a

et al. 2011

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“…This may in part explain why each of the MAPK pathways appears to play some role in the βAR stimulated increase in de novo RNA synthesis. Additionally, Pim-1 has been shown to phosphorylate and stabilize c-myc [39]. Given the established role of c-myc as an activator of RNAP I [40], this may suggest a pathway involving the receptor, PKB and RNAP I being important for rRNA transcription.…”

Section: Discussionmentioning

confidence: 98%

Nuclear β-adrenergic receptors modulate gene expression in adult rat heart

Vaniotis

Duca

Trieu

et al. 2011

Cellular Signalling

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Both β 1 -and β 3 -adrenergic receptors (β 1 ARs and β 3 ARs) are present on nuclear membranes in adult ventricular myocytes. These nuclear-localized receptors are functional with respect to ligand binding and effector activation. In isolated cardiac nuclei, the non-selective βAR agonist isoproterenol stimulated de novo RNA synthesis measured using assays of transcription initiation (Boivin et al., 2006 Cardiovasc Res. 71:69-78). In contrast, stimulation of endothelin receptors, another G protein-coupled receptor (GPCR) that localizes to the nuclear membrane, resulted in decreased RNA synthesis. To investigate the signalling pathway(s) involved in GPCR-mediated regulation of RNA synthesis, nuclei were isolated from intact adult rat hearts and treated with receptor agonists in the presence or absence of inhibitors of different mitogen-activated protein kinase (MAPK) and PI3K/PKB pathways. Components of p38, JNK, and ERK1/2 MAP kinase cascades as well as PKB were detected in nuclear preparations. Inhibition of PKB with triciribine, in the presence of isoproterenol, converted the activation of the βAR from stimulatory to inhibitory with regards to RNA synthesis, while ERK1/2, JNK and p38 inhibition reduced both basal and isoproterenol-stimulated activity. Analysis by qPCR indicated an increase in the expression of 18 S rRNA following isoproterenol treatment and a decrease in NFκB mRNA. Further qPCR experiments revealed that isoproterenol treatment also reduced the expression of several other genes involved in the activation of NFκB, while ERK1/2 and PKB inhibition substantially * Corresponding authors. Hébert is to be contacted

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“…In transgenic form, PIM kinases work as weak oncogenes whereas their oncogenic potential increased when co-expressed with c-Myc (growth regulator factor). [4][5][6][7] Deregulation of c-Myc responsible for disturbance in functions of normal cell which may be a cause of cancer. The current drug development strategies targeted to PIM kinases owing to its role in various hematological malignancies (lymphomas, leukemia, and multiple myeloma) and solid tumors (prostate, colon, pancreatic and other organelles).…”

Section: Introductionmentioning

confidence: 99%

Virtual Screening, Molecular Docking, and DFT Studies of Some Thiazolidine‐2,4‐diones as Potential PIM‐1 Kinase Inhibitors

et al. 2018

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In the present study, ZINC database has been used for virtual screening of thousand of compounds based on previously reported pharmacophore against PIM-1 kinase. These compounds were further screened by Glide docking methodologies such as high throughput virtual screening (HTVS), standard precision (SP) and extra precision (XP), against PIM-1 kinase (PDB ID: 4DTK). Eight top-ranked compounds ZINC22066185, ZINC05678245, ZINC16431468, ZINC05773728, ZINC36633741, ZINC16779084, ZINC19909862 and ZINC15056464, were selected by virtual screening and docking studies. These compounds were showed better binding affinities towards PIM-1 kinase by using amino acid residues such as LYS67, GLU171, ASP128, and ASP186. The top-ranked compounds were showed their predicted binding energies with PIM-1 kinase in the range of À9.06, À8.45, À8.96, À8.78, À8.63, À8.56, À8.56 and À8.30 kcal/mol, respectively. Various reference ligands of PDB ID: 4DTK, 3VBQ and 3VC4, were also taken for docking study on protein kinase (PDB ID: 4DTK) to find out the comparative Glide score of receptor ligand complexes. To confirm the inhibitors potencies, the orbital energies, such as HOMO and LUMO, of the hit compounds were calculated. The results of the study showed that ZINC22066185 and ZINC16779084, may be considered as prototype compounds for further development of potential PIM-1 inhibitors.

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Pim kinase-dependent inhibition of c-Myc degradation

Cited by 219 publications

References 32 publications

The proto-oncogene Pim-1 is a target of miR-33a

The proto-oncogene Pim-1 is a target of miR-33a

Nuclear β-adrenergic receptors modulate gene expression in adult rat heart

Virtual Screening, Molecular Docking, and DFT Studies of Some Thiazolidine‐2,4‐diones as Potential PIM‐1 Kinase Inhibitors

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