The tumor suppressors pRB and p53 as regulators of adipocyte differentiation and function

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) specifically binds and isomerizes the phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif, which leads to changes in protein conformation and function. Pin1 is widely overexpressed in cancers and plays an important role in tumorigenesis. Mounting evidence has revealed that targeting Pin1 is a potential therapeutic approach for various cancers by inhibiting cell proliferation, reducing metastasis, and maintaining genome stability. In this review, we summarize the underlying mechanisms of Pin1-mediated upregulation of oncogenes and downregulation of tumor suppressors in cancer development. Furthermore, we also discuss the multiple roles of Pin1 in cancer hallmarks and examine Pin1 as a desirable pharmaceutical target for cancer therapy. We also summarize the recent progress of Pin1-targeted small-molecule compounds for anticancer activity.

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Biogenesis and Function Mechanisms of Micro-RNAs and Their Role as Oncogenes and Tumor Suppressors

Systems Biology ◽

10.1007/978-4-431-87704-2_19 ◽

2009 ◽

pp. 183-189

Author(s):

Soken Tsuchiya ◽

Kazuya Terasawa ◽

Ryo Kunimoto ◽

Yasushi Okuno ◽

Fumiaki Sato ◽

...

Keyword(s):

Tumor Suppressors ◽

Micro Rnas ◽

And Function

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The Intricate Role of p53 in Adipocyte Differentiation and Function

Cells ◽

10.3390/cells9122621 ◽

2020 ◽

Vol 9 (12) ◽

pp. 2621

Author(s):

Yun Kyung Lee ◽

Yu Seong Chung ◽

Ji Hye Lee ◽

Jin Mi Chun ◽

Jun Hong Park

Keyword(s):

Adipocyte Differentiation ◽

Metabolic Diseases ◽

Metabolic Stress ◽

Health Concern ◽

Metabolic Dysfunction ◽

Direct Role ◽

Proliferation And Apoptosis ◽

Response To Stress ◽

And Function

For more than three decades, numerous studies have demonstrated the function of p53 in cell cycle, cellular senescence, autophagy, apoptosis, and metabolism. Among diverse functions, the essential role of p53 is to maintain cellular homeostatic response to stress by regulating proliferation and apoptosis. Recently, adipocytes have been studied with increasing intensity owing to the increased prevalence of metabolic diseases posing a serious public health concern and because metabolic dysfunction can directly induce tumorigenesis. The prevalence of metabolic diseases has steadily increased worldwide, and a growing interest in these diseases has led to the focus on the role of p53 in metabolism and adipocyte differentiation with or without metabolic stress. However, our collective understanding of the direct role of p53 in adipocyte differentiation and function remains insufficient. Therefore, this review focuses on the newly discovered roles of p53 in adipocyte differentiation and function.

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The Farnesoid X Receptor Regulates Adipocyte Differentiation and Function by Promoting Peroxisome Proliferator-activated Receptor-γ and Interfering with the Wnt/β-Catenin Pathways

Journal of Biological Chemistry ◽

10.1074/jbc.m110.166231 ◽

2010 ◽

Vol 285 (47) ◽

pp. 36759-36767 ◽

Cited By ~ 57

Author(s):

Mouaadh Abdelkarim ◽

Sandrine Caron ◽

Christian Duhem ◽

Janne Prawitt ◽

Julie Dumont ◽

...

Keyword(s):

Adipocyte Differentiation ◽

Farnesoid X Receptor ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

And Function

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SUN-587 IDH1-Dependent Alpha-KG Regulates Brown Fat Differentiation and Function by Modulating Histone Methylation

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1484 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Won Kon Kim ◽

Baek-Soo Han

Keyword(s):

Histone Methylation ◽

Molecular Mechanisms ◽

Adipocyte Differentiation ◽

Uncoupling Protein ◽

Ectopic Expression ◽

Brown Adipocyte ◽

Brown Adipocytes ◽

Brown Adipose ◽

And Function ◽

Brown Adipogenesis

Abstract Brown adipocytes play important roles in the regulation of energy homeostasis by uncoupling protein 1-mediated non-shivering thermogenesis. Recent studies suggest that brown adipocytes as novel therapeutic targets for combating obesity and associated diseases, such as type II diabetes. However, the molecular mechanisms underlying brown adipocyte differentiation and function are not fully understood. We employed previous findings obtained through proteomic studies performed to assess proteins displaying altered levels during brown adipocyte differentiation. Here, we performed assays to determine the functional significance of their altered levels during brown adipogenesis and development. We identified isocitrate dehydrogenase 1 (IDH1) as upregulated during brown adipocyte differentiation, with subsequent investigations revealing that ectopic expression of IDH1 inhibited brown adipogenesis, whereas suppression of IDH1 levels promoted differentiation of brown adipocytes. Additionally, Idh1 overexpression resulted in increased levels of intracellular α-ketoglutarate (α-KG) and inhibited the expression of genes involved in brown adipogenesis. Exogenous treatment with α-KG reduced brown adipogenesis during the early phase of differentiation, and ChIP analysis revealed that IDH1-mediated α-KG reduced trimethylation of histone H3 lysine 4 in the promoters of genes associated with brown adipogenesis. Furthermore, administration of α-KG decreased adipogenic gene expression by modulating histone methylation in brown adipose tissues of mice. These results suggested that the IDH1–α-KG axis plays an important role in regulating brown adipocyte differentiation and might represent a therapeutic target for treating metabolic diseases.

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Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2

Nature Neuroscience ◽

10.1038/nn1566 ◽

2005 ◽

Vol 8 (12) ◽

pp. 1727-1734 ◽

Cited By ~ 303

Author(s):

Sohail F Tavazoie ◽

Veronica A Alvarez ◽

Dennis A Ridenour ◽

David J Kwiatkowski ◽

Bernardo L Sabatini

Keyword(s):

Tumor Suppressors ◽

Neuronal Morphology ◽

And Function

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The role of the orphan nuclear receptor Rev-Erbα in adipocyte differentiation and function

Biochimie ◽

10.1016/j.biochi.2004.12.006 ◽

2005 ◽

Vol 87 (1) ◽

pp. 21-25 ◽

Cited By ~ 37

Author(s):

S Laitinen ◽

C Fontaine ◽

JC Fruchart ◽

B Staels

Keyword(s):

Nuclear Receptor ◽

Adipocyte Differentiation ◽

Orphan Nuclear Receptor ◽

And Function

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TSH stimulates adipogenesis in mouse embryonic stem cells

Journal of Endocrinology ◽

10.1677/joe-07-0452 ◽

2007 ◽

Vol 196 (1) ◽

pp. 159-169 ◽

Cited By ~ 31

Author(s):

Min Lu ◽

Reigh-Yi Lin

Keyword(s):

Adipocyte Differentiation ◽

Es Cells ◽

Embryonic Stem ◽

Binding Activity ◽

Intracellular Camp ◽

Directed Differentiation ◽

Adipose Differentiation ◽

Main Regulator ◽

And Function

Although TSH is the main regulator of thyroid growth and function, TSH binding activity in fat has long been reported. Since the TSH receptor (TSHR) has been detected in both preadipocytes and adipocytes, we hypothesized that it may play a role in adipose differentiation. Here, we use an in vitro model of adipogenesis from mouse embryonic stem (ES) cells to define TSH function. Directed differentiation of ES cells into the adipose lineage can be achieved over a 3-week period. Although adipocyte differentiation is initiated early in the development of cultured ES cells, TSHR up-regulation is precisely correlated with terminal differentiation of those adipocytes. The adipocytes express TSHR on the cell surface and respond to TSH with increased intracellular cAMP production, suggesting the activation of the protein kinase A signaling pathway. To determine whether TSH impacts adipogenesis, we examined how adipocytes responded to TSH at various points during their differentiation from cultured ES cells. We found that TSH greatly increases adipogenesis when added in the presence of adipogenic factors. More importantly, our data suggest that TSH also stimulates adipogenesis in cultured ES cells even in the absence of adipogenic factors. This finding provides the first evidence of TSH being a pro-adipogenic factor that converts ES cells into adipocytes. It further highlights the potential of ES cells as a model system for use in the study of TSH's role in the regulation of physiologically relevant adipose tissue.

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