Crotonylation at serine 46 impairs p53 activity

Liao, Peng; Bhattarai, Nimisha; Cao, Bo; Zhou, Xiang; Jung, Ji Hoon; Damera, Krishna; Fuselier, Taylor; Thareja, Suresh; Wimley, William C.; Wang, Binghe; Zeng, Shelya X.; Lu, Hua

doi:10.1016/j.bbrc.2020.01.152

Cited by 21 publications

(15 citation statements)

References 26 publications

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“…This directly led to reduced p53 level and consequently abnormality in glycolysis pathway and mitochondrial activity. 45 Lysine crotonylation plays an inhibitory role in the development and metastasis of hepatocellular carcinoma. 46 Sirtuin family members SIRT1, SIRT2, and SIRT3 are responsible for the removal of histone H3K4 crotonylation in vitro.…”

Section: Protein-acylation Modificationmentioning

confidence: 99%

Insights into the post-translational modification and its emerging role in shaping the tumor microenvironment

Wen

Zhang

et al. 2021

Sig Transduct Target Ther

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More and more in-depth studies have revealed that the occurrence and development of tumors depend on gene mutation and tumor heterogeneity. The most important manifestation of tumor heterogeneity is the dynamic change of tumor microenvironment (TME) heterogeneity. This depends not only on the tumor cells themselves in the microenvironment where the infiltrating immune cells and matrix together forming an antitumor and/or pro-tumor network. TME has resulted in novel therapeutic interventions as a place beyond tumor beds. The malignant cancer cells, tumor infiltrate immune cells, angiogenic vascular cells, lymphatic endothelial cells, cancer-associated fibroblastic cells, and the released factors including intracellular metabolites, hormonal signals and inflammatory mediators all contribute actively to cancer progression. Protein post-translational modification (PTM) is often regarded as a degradative mechanism in protein destruction or turnover to maintain physiological homeostasis. Advances in quantitative transcriptomics, proteomics, and nuclease-based gene editing are now paving the global ways for exploring PTMs. In this review, we focus on recent developments in the PTM area and speculate on their importance as a critical functional readout for the regulation of TME. A wealth of information has been emerging to prove useful in the search for conventional therapies and the development of global therapeutic strategies.

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Section: Protein-acylation Modificationmentioning

confidence: 99%

Insights into the post-translational modification and its emerging role in shaping the tumor microenvironment

Wen

Zhang

et al. 2021

Sig Transduct Target Ther

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“…Similarity to acetylation, whether crotonylation is associated with protein degradation or not? Liao et al reported that crotonic acid induced the crotonylation of p53 and thus affected its degradation [10] (Figure 7D). Yet, the degradation pathways that were involved in the regulation of p53 degradation have not been identified.…”

Section: Protein Degradationmentioning

confidence: 93%

“…The crotonylation of HDAC1 was enhanced by NaCr and the crotonylated HDAC1 exhibited reduction in its deacetylase activity compared with unmodified HDAC1 (Figure 7A). Also, p53 was found to be crotonylated at serine 46 after crotonic acid treatment that led to the inhibition of p53 activity in a dose-dependent fashion [10]. The crotonylation of p53 lowered the activity of p53 protein to enhance the p53-dependent glycolytic activity and the proliferation of cancer cells in response to stress from metabolism or DNA damage [10] (Figure 7B).…”

Section: Protein Activitymentioning

confidence: 99%

“…Lysine crotonylation (Kcr) is one of histone lysine acylation modifications [6]. Crotonylation mainly occurs on the ε-amino group of lysine in histones and was recently reported to occurs on serine residue [10]. As mass spectrometry and proteomics developed, the existence of crotonylation has been confirmed in various microorganism (bacteria and fungus), plants and animals [11][12][13].…”

Section: Ivyspring International Publishermentioning

confidence: 99%

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The Function and related Diseases of Protein Crotonylation

Wang¹,

Mu²,

Qiu³

et al. 2021

Int. J. Biol. Sci.

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Crotonylation is a kind of newly discovered acylation modification. Thousands of crotonylation sites have been identified in histone and non-histone proteins over the past decade. As a modification closely related to acetylation, crotonylation was reported to share many universal enzymes with acetylation. Crotonylated proteins have important roles in the regulation of various biological processes, such as gene expression, process of spermatogenesis, cell cycle, and also in the pathogenesis of different diseases, which range from depression to cancer. In this review, we summarize the research processes of crotonylation and discuss the advances of regulation mechanism of both histone and non-histone proteins crotonylation in difference physiological processes. Also, we focus on the alteration of the crotonylation under certain pathological conditions and its role in the pathogenesis of each disease.

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“…Moreover, novel modifications of p53 have been successively verified. Crotonylation occurs at S46 of p53 in response to crotonic acid, which induces glycolytic activity and promotes cancer cell growth ( Liao et al, 2020 ). Upon β-hydroxybutyrate (BHB) treatment, p300/CBP-mediated β-hydroxybutyrylation (Kbhb) occurs at K120, K319, and K370 of p53, which impairs the transcriptional activity of p53 due to the attenuated acetylation level ( Liu et al, 2019a ).…”

Section: The Ptm Code and Its Functional Readout For P53mentioning

confidence: 99%

Deciphering the PTM codes of the tumor suppressor p53

Wen

Wang

2021

Journal of Molecular Cell Biology

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The genome guardian p53 functions as a transcription factor that senses numerous cellular stresses and orchestrates the corresponding transcriptional events involved in determining various cellular outcomes, including cell cycle arrest, apoptosis, senescence, DNA repair, and metabolic regulation. In response to diverse stresses, p53 undergoes multiple posttranslational modifications (PTMs) that coordinate with intimate interdependencies to precisely modulate its diverse properties in given biological contexts. Notably, PTMs can recruit ‘reader’ proteins that exclusively recognize specific modifications and facilitate the functional readout of p53. Targeting PTM‒reader interplay has been developing into a promising cancer therapeutic strategy. In this review, we summarize the advances in deciphering the ‘PTM codes’ of p53, focusing particularly on the mechanisms by which the specific reader proteins functionally decipher the information harbored within these PTMs of p53. We also highlight the potential applications of intervention with p53 PTM‒reader interactions in cancer therapy and discuss perspectives on the ‘PTMomic’ study of p53 and other proteins.

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Crotonylation at serine 46 impairs p53 activity

Cited by 21 publications

References 26 publications

Insights into the post-translational modification and its emerging role in shaping the tumor microenvironment

Insights into the post-translational modification and its emerging role in shaping the tumor microenvironment

The Function and related Diseases of Protein Crotonylation

Deciphering the PTM codes of the tumor suppressor p53

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