PPARγ ligand production is tightly linked to clonal expansion during initiation of adipocyte differentiation

Hallenborg, Philip; Petersen, Rasmus Koefoed; Feddersen, Søren; Sundekilde, Ulrik Kræmer; Hansen, Jacob B.; Blagoev, Blagoy; Madsen, Lise; Kristiansen, Karsten

doi:10.1194/jlr.m050658

Cited by 25 publications

(21 citation statements)

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“…In general, it is believed that p53 negatively regulates white adipocyte differentiation [413][414][415]. Hallenborg et al showed that MEFs deficient in either the transcription factor p53 or its target gene encoding the cyclin-dependent kinase inhibitor p21, exhibited increased adipogenic potential [416].Huang et al [415] found that p53 expression increased on the second and fourth day of 3T3-L1adipocyte differentiation and decreased thereafter. p53 activity is weakened in the abdominal adipose tissue in diet-induced obese rats because of its reduced phosphorylation [415].Over-expression of p53 in 3T3-L1 preadipocytes markedly reduced adipogenesis and marker geneexpression [415].…”

Section: P53 and Adipocyte Differentiationmentioning

confidence: 98%

Redox modulation of adipocyte differentiation: hypothesis of “Redox Chain” and novel insights into intervention of adipogenesis and obesity

Wang

Hai

2015

Free Radical Biology and Medicine

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Section: P53 and Adipocyte Differentiationmentioning

confidence: 98%

Redox modulation of adipocyte differentiation: hypothesis of “Redox Chain” and novel insights into intervention of adipogenesis and obesity

Wang

Hai

2015

Free Radical Biology and Medicine

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“…Gene Expression Analyses-Total RNA was prepared as previously described (48). Briefly, RNA was purified from Kit225 T cells using TRIzol (Invitrogen) according to manufacturerЈs instructions.…”

Section: Reagentsmentioning

confidence: 99%

Nuclear Phosphoproteomic Screen Uncovers ACLY as Mediator of IL-2-induced Proliferation of CD4+ T lymphocytes

Osinalde

Mitxelena

Sanchez-Quiles

et al. 2016

Molecular & Cellular Proteomics

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Anti-cancer immunotherapies commonly rely on the use of interleukin-2 (IL-2) to promote the expansion of T lymphocytes. IL-2-dependent proliferation is the culmination of a complex network of phosphorylation-driven signaling events that impact on gene transcription through mechanisms that are not clearly understood. To study the role of IL-2 in the regulation of nuclear protein function we have performed an unbiased mass spectrometry-based study of the nuclear phosphoproteome of resting and IL-2-treated CD4 ؉ T lymphocytes. We detected 8521distinct phosphosites including many that are not yet reported in curated phosphorylation databases. Although most phosphorylation sites remained unaffected upon IL-2 treatment, 391 sites corresponding to 288 gene products showed robust IL-2-dependent regulation. Importantly, we show that ATP-citrate lyase (ACLY) is a key phosphoprotein effector of IL-2-mediated T-cell responses. ACLY becomes phosphorylated on serine 455 in T lymphocytes upon IL-2-driven activation of AKT, and depletion or inactivation of ACLY compromises IL-2-promoted T-cell growth. Mechanistically, we demonstrate that ACLY is required for enhancing histone acetylation levels and inducing the expression of cell cycle regulating genes in response to IL-2. Thus, the metabolic enzyme ACLY emerges as a bridge between cytokine signaling and proliferation of T lymphocytes, and may be an attractive candidate target for the development of more efficient anti-cancer The underlying principle of cancer immunotherapy is to eliminate malignant cells by tuning the immune system (1-2). This revolutionary way of fighting tumors was originated three decades ago when a patient suffering from metastatic melanoma was treated with the T-cell growth promoting factor interleukin-2 (IL-2) 1 (3). The success of IL-2 administration in fighting metastatic melanoma demonstrated for the first time that solely potentiating the activation of T lymphocytes could abrogate certain human cancers (4). Current immunotherapy approaches include the use of autologous gene-engineered T cells that, once expanded ex vivo with IL-2, are re-infused back into patients by the so-called adoptive cell transfer therapy (ACT) (5-7). Despite the promising results of this approach, a safe and long-lasting expansion of transferred T cells remains a major challenge because of the undesirable side effects derived from the use of IL-2. Continued exposure to high doses of IL-2 results in increased susceptibility of T cells to apoptosis (8). Moreover, IL-2 is also a critical component for regulatory T-cell (T reg ) development and function (9 -10), and as such it functions as a negative regulator of the immune response (11). Consequently, although IL-2 constitutes a key component of current immunotherapies, a great deal of effort is being devoted to the development of novel strategies that would boost the T-cell immune response more safely. In this regard, it has been shown that IL-2-related toxicity can be partially minimized by the use of gene-engineered T cells ex...

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“…Unlike most cell types that express cdk2 throughout the cell cycle including G 1, 3T3-L1 preadipocytes do not express cdk2 in the G 1 phase of MCE (Montagnoli et al 1999). incorporation into DNA and failure to proliferate (Hallenborg et al 2014). These findings support the notion that MCE is a prerequisite for adipogenesis.…”

Section: Akt and Mcesupporting

confidence: 67%

“…xanthine oxidoreductase (XOR) (Hallenborg et al 2014)It has been proposed that lipid autooxidation by ROS generated by XOR then results in the production of substrates for eLOX3 which then converts the peroxidized lipids into hepoxilin-like products that function as endogenous PPARγ agonists (Hallenborg et al 2014). An eLOX3 inhibitor, baicalein, decreases PPARγ ligand generation (Madsen at al.…”

Section: Erk and Mcementioning

confidence: 99%

The Effects of Artemisia Derived Natural Products on Adipogenesis

Abood¹

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PPARγ ligand production is tightly linked to clonal expansion during initiation of adipocyte differentiation

Cited by 25 publications

References 50 publications

Redox modulation of adipocyte differentiation: hypothesis of “Redox Chain” and novel insights into intervention of adipogenesis and obesity

Redox modulation of adipocyte differentiation: hypothesis of “Redox Chain” and novel insights into intervention of adipogenesis and obesity

Nuclear Phosphoproteomic Screen Uncovers ACLY as Mediator of IL-2-induced Proliferation of CD4+ T lymphocytes

The Effects of Artemisia Derived Natural Products on Adipogenesis

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