Histone methyltransferase SMYD2: ubiquitous regulator of disease

Yi, Xin; Jiang, Xuejun; Fang, Zemin

doi:10.1186/s13148-019-0711-4

Cited by 69 publications

(78 citation statements)

References 84 publications

(154 reference statements)

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“…Protein methylation usually occurs on lysine or arginine, and both histones and nonhistone proteins can be methylated [ 104 – 106 ]. A plethora of studies have demonstrated that protein methylation plays an important role in cell survival/death and diseases [ 104 , 107 – 109 ], but the research on their roles in ferroptosis is in its infancy. For example, lysine demethylase 3B (KDM3B), a histone H3K9 demethylase, inhibits erastin-induced ferroptosis by cooperating with the transcription factor activating transcription factor 4 (ATF4) to upregulate SLC7A11 expression [ 110 ] ( Figure 4 ).…”

Section: Posttranslational Modifications (Ptms) In Ferroptosismentioning

confidence: 99%

Posttranslational Modifications in Ferroptosis

Wei

Zhu

et al. 2020

Oxidative Medicine and Cellular Longevity

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130

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Ferroptosis was first coined in 2012 to describe the form of regulated cell death (RCD) characterized by iron-dependent lipid peroxidation. To date, ferroptosis has been implicated in many diseases, such as carcinogenesis, degenerative diseases (e.g., Huntington’s, Alzheimer’s, and Parkinson’s diseases), ischemia-reperfusion injury, and cardiovascular diseases. Previous studies have identified numerous targets involved in ferroptosis; for example, acyl-CoA synthetase long-chain family member 4 (ACSL4) and p53 induce while glutathione peroxidase 4 (GPX4) and apoptosis-inducing factor mitochondria-associated 2 (AIFM2, also known as FSP1) inhibit ferroptosis. At least three major pathways (the glutathione-GPX4, FSP1-coenzyme Q10 (CoQ10), and GTP cyclohydrolase-1- (GCH1-) tetrahydrobiopterin (BH4) pathways) have been identified to participate in ferroptosis regulation. Recent advances have also highlighted the crucial roles of posttranslational modifications (PTMs) of proteins in ferroptosis. Here, we summarize the recently discovered knowledge regarding the mechanisms underlying ferroptosis, particularly the roles of PTMs in ferroptosis regulation.

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Section: Posttranslational Modifications (Ptms) In Ferroptosismentioning

confidence: 99%

Posttranslational Modifications in Ferroptosis

Wei

Zhu

et al. 2020

Oxidative Medicine and Cellular Longevity

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130

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“…Most of the data concerning the relationship between SMYD2 and the immune system refer to its methyltransferase activity on histone 3 lysine 36 (H3K36) (Brown et al 2006). Nonetheless, SMYD2 enzymatic activity is not restricted to H3K36, and this enzyme can also act on histone 4 lysine 20 (H4K20), among other targets (Boehm et al 2017;Yi, Jiang, and Fang 2019).…”

Section: Smyd2mentioning

confidence: 99%

“…These enzymes act on histone and nonhistone targets to regulate many biological processes, including muscle development and cancer (Spellmon et al 2015). Indeed, SMYD2 (Yi, Jiang, and Fang 2019) and SMYD3 (Bottino et al 2020) are considered to have oncogenic properties in a myriad of cancer types, although they are dispensable for normal mouse development and adult life, probably due to its redundancy (Bagislar et al 2016). In addition, SMYD proteins are very important for muscle physiopathology (Du, Tan, and Zhang 2014).…”

Section: Introductionmentioning

confidence: 99%

The SMYD family proteins in immunology

Rubio-Tomás

2021

Preprint

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Epigenetics is an emerging field, due to its relevance in the regulation of a wide range of biological processes. The Su(Var)3-9, Enhancer-of-zeste and Trithorax (SET) and Myeloid, Nervy, and DEAF-1 (MYND) domain-containing (SMYD) proteins, named SMYD1, SMYD2, SMYD3, SMYD4 and SMYD5, are enzymes that catalyse methylation of histone and non-histone substrates, thereby playing a key role in gene expression regulation in many biological contexts, such as muscle development and physiology, haematopoiesis and many types of cancer. This review focuses on a relatively unexplored aspect of SMYD family members - their relation with immunology. Here, immunology is defined in the broadest sense of the word, including basic research on macrophage function or host immunity against pathogen infection, as well as clinical studies, most of which are centred on blood cancers.

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“…SMYD2 is essential for normal organismal development and dysregulation of SMYD2 was found in cardiovascular disease and cancer . For example, SMYD2 is significantly overexpressed in many cancers including esophageal squamous cell carcinoma (ESCC), bladder and gastric cancer, and in triple negative breast cancer it was shown to have a tumor promoting effect . In some cases, the molecular mechanisms connecting the methylation of SMYD2 non‐histone substrates and oncogenic effects have been discovered and, based on these, inhibitors of SMYD2 have been tested as therapeutic agents …”

Section: Introductionmentioning

confidence: 99%

Analysis of the Substrate Specificity of the SMYD2 Protein Lysine Methyltransferase and Discovery of Novel Non‐Histone Substrates

et al. 2019

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The SMYD2 protein lysine methyltransferase methylates various histone and non‐histone proteins and is overexpressed in several cancers. Using peptide arrays, we investigated the substrate specificity of the enzyme, revealing a recognition of leucine (or weaker phenylalanine) at the −1 peptide site and disfavor of acidic residues at the +1 to +3 sites. Using this motif, novel SMYD2 peptide substrates were identified, leading to the discovery of 32 novel peptide substrates with a validated target site. Among them, 19 were previously reported to be methylated at the target lysine in human cells, strongly suggesting that SMYD2 is the protein lysine methyltransferase responsible for this activity. Methylation of some of the novel peptide substrates was tested at the protein level, leading to the identification of 14 novel protein substrates of SMYD2, six of which were more strongly methylated than p53, the best SMYD2 substrate described so far. The novel SMYD2 substrate proteins are involved in diverse biological processes such as chromatin regulation, transcription, and intracellular signaling. The results of our study provide a fundament for future investigations into the role of this important enzyme in normal development and cancer.

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Histone methyltransferase SMYD2: ubiquitous regulator of disease

Cited by 69 publications

References 84 publications

Posttranslational Modifications in Ferroptosis

Posttranslational Modifications in Ferroptosis

The SMYD family proteins in immunology

Analysis of the Substrate Specificity of the SMYD2 Protein Lysine Methyltransferase and Discovery of Novel Non‐Histone Substrates

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