Full Text Journal Articles by
Author Tihomir Miralem

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Interaction of human biliverdin reductase with Akt/protein kinase B and phosphatidylinositol-dependent kinase 1 regulates glycogen synthase kinase 3 activity: a novel mechanism of Akt activation.

Tihomir Miralem, Nicole Lerner-Marmarosh, Peter E M Gibbs, Jermaine L Jenkins, Chelsea Heimiller, Mahin D Maines,

Biliverdin reductase A (BVR) and Akt isozymes have overlapping pleiotropic functions in the insulin/PI3K/MAPK pathway. Human BVR (hBVR) also reduces the hemeoxygenase activity product biliverdin to bilirubin and is directly activated by insulin receptor kinase (IRK). Akt isoenzymes (Akt1-3) are downstream of IRK and are activated by phosphatidylinositol-dependent kinase 1 ... Read more >>

FASEB J. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2016, 30(8):2926-2944]

Cited: 12 times

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Biliverdin reductase: a target for cancer therapy?

Peter E M Gibbs, Tihomir Miralem, Mahin D Maines,

Biliverdin reductase (BVR) is a multifunctional protein that is the primary source of the potent antioxidant, bilirubin. BVR regulates activities/functions in the insulin/IGF-1/IRK/PI3K/MAPK pathways. Activation of certain kinases in these pathways is/are hallmark(s) of cancerous cells. The protein is a scaffold/bridge and intracellular transporter of kinases that regulate growth and ... Read more >>

(Frontiers in pharmacology)
[2015, 6:119]

Cited: 13 times

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Renal capsule xenografting and subcutaneous pellet implantation for the evaluation of prostate carcinogenesis and benign prostatic hyperplasia.

Tristan M Nicholson, Kristen S Uchtmann, Conrad D Valdez, Ashleigh B Theberge, Tihomir Miralem, William A Ricke,

New therapies for two common prostate diseases, prostate cancer (PrCa) and benign prostatic hyperplasia (BPH), depend critically on experiments evaluating their hormonal regulation. Sex steroid hormones (notably androgens and estrogens) are important in PrCa and BPH; we probe their respective roles in inducing prostate growth and carcinogenesis in mice with ... Read more >>

J Vis Exp (Journal of visualized experiments : JoVE)
[2013, (78):]

Cited: 4 times

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Formation of ternary complex of human biliverdin reductase-protein kinase Cδ-ERK2 protein is essential for ERK2-mediated activation of Elk1 protein, nuclear factor-κB, and inducible nitric-oxidase synthase (iNOS).

Peter E M Gibbs, Tihomir Miralem, Nicole Lerner-Marmarosh, Cicerone Tudor, Mahin D Maines,

Growth factors, insulin, oxidative stress, and cytokines activate ERK1/2 by PKCδ and MEK1/2. Human biliverdin reductase (hBVR), a Ser/Thr/Tyr kinase and intracellular scaffold/bridge/anchor, is a nuclear transporter of MEK1/2-stimulated ERK1/2 (Lerner-Marmarosh, N., Miralem, T., Gibbs, P. E., and Maines, M. D. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 6870-6875). hBVR, ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2012, 287(2):1066-1079]

Cited: 16 times

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Characterization of the human biliverdin reductase gene structure and regulatory elements: promoter activity is enhanced by hypoxia and suppressed by TNF-alpha-activated NF-kappaB.

Peter E M Gibbs, Tihomir Miralem, Mahin D Maines,

hBVR is a Ser/Thr/Tyr kinase/scaffold protein/transcription factor/intracellular transporter of regulators. hBVR is an upstream activator of the insulin/IGF-1/MAPK/PI3K signaling pathway, and of NF-kappaB. As a reductase, it converts biliverdin to the antioxidant, bilirubin. hBVR gene has 8 exons; exon 1 is not translated. We report the characterization of hBVR promoter ... Read more >>

FASEB J. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2010, 24(9):3239-3254]

Cited: 14 times

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Human biliverdin reductase suppresses Goodpasture antigen-binding protein (GPBP) kinase activity: the reductase regulates tumor necrosis factor-alpha-NF-kappaB-dependent GPBP expression.

Tihomir Miralem, Peter E M Gibbs, Fernando Revert, Juan Saus, Mahin D Maines,

The Ser/Thr/Tyr kinase activity of human biliverdin reductase (hBVR) and the expression of Goodpasture antigen-binding protein (GPBP), a nonconventional Ser/Thr kinase for the type IV collagen of basement membrane, are regulated by tumor necrosis factor (TNF-alpha). The pro-inflammatory cytokine stimulates kinase activity of hBVR and activates NF-kappaB, a transcriptional regulator ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2010, 285(17):12551-12558]

Cited: 8 times

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Human biliverdin reductase is an ERK activator; hBVR is an ERK nuclear transporter and is required for MAPK signaling.

Nicole Lerner-Marmarosh, Tihomir Miralem, Peter E M Gibbs, Mahin D Maines,

Activation of the MEK/ERK/Elk-signaling cascade is a mechanism for relaying mitogenic and stress stimuli for gene activation. MEK1 is the proximate kinase for activation of ERK1/2, and nuclear targeting of ERK1/2 is obligatory for Elk1 transcriptional activity. Human biliverdin reductase (hBVR) is a recently described Ser/Thr/Tyr kinase in the MAPK ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2008, 105(19):6870-6875]

Cited: 54 times

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Human biliverdin reductase, a previously unknown activator of protein kinase C betaII.

Mahin D Maines, Tihomir Miralem, Nicole Lerner-Marmarosh, Jenny Shen, Peter E M Gibbs,

Human biliverdin reductase (hBVR), a dual specificity kinase (Ser/Thr/Tyr) is, as protein kinase C (PKC) betaII, activated by insulin and free radicals (Miralem, T., Hu, Z., Torno, M. D., Lelli, K. M., and Maines, M. D. (2005) J. Biol. Chem. 280, 17084-17092; Lerner-Marmarosh, N., Shen, J., Torno, M. D., Kravets, ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2007, 282(11):8110-8122]

Cited: 29 times

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Regulation of TNF-alpha-activated PKC-zeta signaling by the human biliverdin reductase: identification of activating and inhibitory domains of the reductase.

Nicole Lerner-Marmarosh, Tihomir Miralem, Peter E M Gibbs, Mahin D Maines,

Human biliverdin reductase (hBVR) is a dual function enzyme: a catalyst for bilirubin formation and a S/T/Y kinase that shares activators with protein kinase C (PKC) -zeta, including cytokines, insulin, and reactive oxygen species (ROS). Presently, we show that hBVR increases PKC-zeta autophosphorylation, stimulation by TNF-alpha, as well as cytokine ... Read more >>

FASEB J. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2007, 21(14):3949-3962]

Cited: 27 times

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Small interference RNA-mediated gene silencing of human biliverdin reductase, but not that of heme oxygenase-1, attenuates arsenite-mediated induction of the oxygenase and increases apoptosis in 293A kidney cells.

Tihomir Miralem, Zhenbo Hu, Michael D Torno, Katherine M Lelli, Mahin D Maines,

BVR reduces biliverdin, the HO-1 and HO-2 product, to bilirubin. Human biliverdin (BVR) is a serine/threonine kinase activated by free radicals. It is a leucine zipper (bZip) DNA-binding protein and a regulatory factor for 8/7-bp AP-1-regulated genes, including HO-1 and ATF-2/CREB. Presently, small interference (si) RNA constructs were used to ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2005, 280(17):17084-17092]

Cited: 61 times

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Biliverdin reductase, a novel regulator for induction of activating transcription factor-2 and heme oxygenase-1.

Anatoliy Kravets, Zhenbo Hu, Tihomir Miralem, Michael D Torno, Mahin D Maines,

Biliverdin IXalpha reductase (BVR) catalyzes reduction of the HO activity product, biliverdin, to bilirubin. hBVR is a serine/threonine kinase that contains a bZip domain. Presently, regulation of gene expression by hBVR was examined. 293A cells were infected with adenovirus-doxycycline (Ad-Dox)-inducible hBVR cDNA. High level expression of hBVR was determined at ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2004, 279(19):19916-19923]

Cited: 61 times

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