ATRA transcriptionally induces nSMase2 through CBP/p300-mediated histone acetylation

Clarke, Christopher J.; Shamseddine, A.; Jacob, J.; Khalife, Gabrielle; Burns, Tara A.; Hannun, Yusuf A.

doi:10.1194/jlr.m067447

Cited by 21 publications

(14 citation statements)

References 48 publications

(93 reference statements)

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“…Neutral sphingomyelinase 2 (nSMase2) is regulated at the mRNA level by p53 in the context of the DNA damage response (DDR) or by epigenetic mechanisms, including a combination of DNA methylation and histone deacetylation, with histone deacetylation mediating induction by all- trans retinoic acid (ATRA) 70,157 . It is also regulated by serine phosphorylation promoted by reactive oxygen species (ROS) and tumour necrosis factor (TNF) signalling 165 .…”

Section: Sphingolipid Metabolismmentioning

confidence: 99%

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Sphingolipids and their metabolism in physiology and disease

Hannun

Obeid

2017

Nat Rev Mol Cell Biol

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1,462

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Studies of bioactive lipids in general and sphingolipids in particular have intensified over the past several years, revealing an unprecedented and unanticipated complexity of the lipidome and its many functions, which rivals, if not exceeds, that of the genome or proteome. These results highlight critical roles for bioactive sphingolipids in most, if not all, major cell biological responses, including all major cell signalling pathways, and they link sphingolipid metabolism to key human diseases. Nevertheless, the fairly nascent field of bioactive sphingolipids still faces challenges in its biochemical and molecular underpinnings, including defining the molecular mechanisms of pathway and enzyme regulation, the study of lipid-protein interactions and the development of cellular probes, suitable biomarkers and therapeutic approaches.

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Section: Sphingolipid Metabolismmentioning

confidence: 99%

“…Accordingly, in chondrocytes, nSMase2 was demonstrated to be a downstream target for bone morphogenetic protein 2 (REF. 155) and for all- trans retinoic acid (ATRA) 156,157 , key regulators of bone and cartilage development.…”

Section: Roles In (Patho)physiologymentioning

confidence: 99%

Sphingolipids and their metabolism in physiology and disease

Hannun

Obeid

2017

Nat Rev Mol Cell Biol

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1,462

1,396

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“…The long fatty chain of TSA bound to the inner part of the tubular bag, and the hydroxime group at the end of the fatty chain showed connection with the zinc binding region through carbonyl and hydroxyl groups, which thereby inhibiting the ability of HDACs including recognizing substrate, regulating enzymatic activity and interacting with other proteins ( 128 ). TSA was illustrated to inhibit HDAC5 to block malignant behavior of cancer cells, including chemoresistance ( 120 ), proliferation ( 124 ) and invasion ( 25 ). Other HDACis such as belinostat, givenostat, panobinostat and dacinostat have the same mechanism with TSA as well.…”

Section: Clinical Significance Of Hdac5 In Cancermentioning

confidence: 99%

Insights Into the Function and Clinical Application of HDAC5 in Cancer Management

Yang

Gong

et al. 2021

Front. Oncol.

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Histone deacetylase 5 (HDAC5) is a class II HDAC. Aberrant expression of HDAC5 has been observed in multiple cancer types, and its functions in cell proliferation and invasion, the immune response, and maintenance of stemness have been widely studied. HDAC5 is considered as a reliable therapeutic target for anticancer drugs. In light of recent findings regarding the role of epigenetic reprogramming in tumorigenesis, in this review, we provide an overview of the expression, biological functions, regulatory mechanisms, and clinical significance of HDAC5 in cancer.

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“…Although the mechanism of action is still unknown, studies have demonstrated that tretinoin encourages progenitor cells in APL patients to differentiate terminally and thereby ameliorating the progression of the disease [58]. A recent study identified nSMase2 as an early ATRA-induced gene and implicated nSMase2 having a role in growth arrest after ATRA treatment [59]. Furthermore, it was found that ATRA regulates nSMase2 directly through modulation of histone acetylation in a CREB-binding protein and p300 dependent manner [59].…”

Section: Epigenetic Regulators Of Sphingolipid Metabolismmentioning

confidence: 99%

“…A recent study identified nSMase2 as an early ATRA-induced gene and implicated nSMase2 having a role in growth arrest after ATRA treatment [59]. Furthermore, it was found that ATRA regulates nSMase2 directly through modulation of histone acetylation in a CREB-binding protein and p300 dependent manner [59].…”

Section: Epigenetic Regulators Of Sphingolipid Metabolismmentioning

confidence: 99%

Epigenetics and Sphingolipid Metabolism in Health and Disease

et al. 2018

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Sphingolipids represent one of the major classes of bioactive lipids. Studies of sphingolipids have intensified in the past several years, revealing their roles in nearly all cell biological processes. In addition, epigenetic regulation has gained substantial interest due to its role in controlling gene expression and activity without changing the genetic code. In this review, we first introduce a brief background on sphingolipid biology, highlighting its role in pathophysiology. We then illustrate the concept of epigenetic regulation, focusing on how it affects the metabolism of sphingolipids. We further discuss the roles of bioactive sphingolipids as epigenetic regulators themselves. Overall, a better understanding of the relationship between epigenetics and sphingolipid metabolism may help to improve the development of sphingolipid-targeted therapeutics.

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ATRA transcriptionally induces nSMase2 through CBP/p300-mediated histone acetylation

Cited by 21 publications

References 48 publications

Sphingolipids and their metabolism in physiology and disease

Sphingolipids and their metabolism in physiology and disease

Insights Into the Function and Clinical Application of HDAC5 in Cancer Management

Epigenetics and Sphingolipid Metabolism in Health and Disease

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