Calcium‐dependent methylation by PRMT1 promotes erythroid differentiation through the p38α MAPK pathway

Liu, Mei Yin; Hua, Wei; Chiou, Yi Ying; Chen, Chi Ju; Yao, Chao‐Ling; Lai, Yi Ting; Chao, Lin; Lin, Wey Jinq

doi:10.1002/1873-3468.13614

Cited by 8 publications

(10 citation statements)

References 50 publications

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“…However, the upstream signalling pathway that activates PRMT1 is still not clear. In addition, H 2 O 2 and Ca 2+ signals have been reported to enhance the activity of PRMT1 25,36 . Additional studies are needed to define the mechanism by which methylation at these residues could affect TSC disease pathology and whether activation or inhibition of PRMT1 could be an effective strategy to mitigate the symptoms of TSC disease.…”

Section: Discussionmentioning

confidence: 99%

Stability of tuberous sclerosis complex 2 is controlled by methylation at R1457 and R1459

Gen

Kobayashi

et al. 2020

Sci Rep

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Mutations in genes that encode components of tuberous sclerosis complex 2 (TSC2) are associated with tuberous sclerosis complex disease. TSC2 interacts with tuberous sclerosis complex 1 to form a complex that negatively regulates cell growth and proliferation via the inactivation of mechanistic target of rapamycin complex 1. The activity of TSC2 is mainly regulated via posttranslational modifications such as phosphorylation. However, the control of TSC2 activity is not entirely achieved by phosphorylation. In this study, we show that TSC2 is methylated at R1457 and R1459 by protein arginine methyltransferase 1 (PRMT1). Methylation of these two residues can affect the phosphorylation status through protein kinase B (Akt) of TSC2 at T1462 and is essential for TSC2 stability. Taken together, these findings indicate that novel posttranslational modifications are important for the regulation of TSC2 stability through PRMT1-mediated methylation.

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Section: Discussionmentioning

confidence: 99%

Stability of tuberous sclerosis complex 2 is controlled by methylation at R1457 and R1459

Gen

Kobayashi

et al. 2020

Sci Rep

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“…The hypothesis is that Ca 2+ selectively regulates signaling pathways due to its wide range of binding proteins. Liu et al were able to show the regulatory mechanism that demonstrates how PRMT1 modulates the MAPK pathway in response to Ca 2+ [91]. Ca 2+ stimulation significantly enhanced protein methyltransferase PRMT1 activity in cells and enhanced Arac-induced erythroid differentiation (80% at 96 h), whereas a pharmacological activator of p38 MAPKs, SB203580, completely diminished Arac-induced erythroid differentiation, indicating that the MAPK (p38) signaling pathway plays a crucial role in Ca 2+ -mediated signaling.…”

Section: Prmt1 and Cancer/inflammationmentioning

confidence: 99%

DNA or Protein Methylation-Dependent Regulation of Activator Protein-1 Function

Kim

Ahuja

Kim

et al. 2021

Cells

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Epigenetic regulation and modification govern the transcriptional mechanisms that promote disease initiation and progression, but can also control the oncogenic processes, cell signaling networks, immunogenicity, and immune cells involved in anti-inflammatory and anti-tumor responses. The study of epigenetic mechanisms could have important implications for the development of potential anti-inflammatory treatments and anti-cancer immunotherapies. In this review, we have described the key role of epigenetic progression: DNA methylation, histone methylation or modification, and protein methylation, with an emphasis on the activator protein-1 (AP-1) signaling pathway. Transcription factor AP-1 regulates multiple genes and is involved in diverse cellular processes, including survival, differentiation, apoptosis, and development. Here, the AP-1 regulatory mechanism by DNA, histone, or protein methylation was also reviewed. Various methyltransferases activate or suppress AP-1 activities in diverse ways. We summarize the current studies on epigenetic alterations, which regulate AP-1 signaling during inflammation, cancer, and autoimmune diseases, and discuss the epigenetic mechanisms involved in the regulation of AP-1 signaling.

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“…The human chronic myelogenous leukemia (CML) K562 cells were purchased from BCRC (Bioresource Collection and Research Center, Hsinchu, Taiwan) and cultured in RPMI1640 media containing 10% FBS as described [38]. KBM5 cells were obtained from Bing E. Carter (The University of Texas MD Anderson Cancer Center, Houston, TX, USA) and cultured in IMDM media containing 10% FBS.…”

Section: Cell Culturementioning

confidence: 99%

Perturbation of p38α MAPK as a Novel Strategy to Effectively Sensitize Chronic Myeloid Leukemia Cells to Therapeutic BCR-ABL Inhibitors

Kuo

Wei

Jiang

et al. 2021

IJMS

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Chronic myeloid leukemia (CML) is a hematopoietic malignancy characterized by the presence of the BCR-ABL oncogene. Therapeutic regimens with tyrosine kinase inhibitors (TKIs) specifically targeting BCR-ABL have greatly improved overall survival of CML. However, drug intolerance and related toxicity remain. Combined therapy is effective in reducing drug magnitude while increasing therapeutic efficacy and, thus, lowers undesired adverse side effects. The p38 MAPK activity is critically linked to the pathogenesis of a number of diseases including hematopoietic diseases; however, the role of each isozyme in CML and TKI-mediated effects is still elusive. In this study, we used specific gene knockdown to clearly demonstrate that the deficiency of p38α greatly enhanced the therapeutic efficacy in growth suppression and cytotoxicity of TKIs, first-generation imatinib, and second generation dasatinib by approximately 2.5–3.0-fold in BCR-ABL-positive CML-derived leukemia K562 and KMB5 cells. Knockdown of p38β, which displays the most sequence similarity to p38α, exerted distinct and opposite effects on the TKI-mediated therapeutic efficacy. These results show the importance of isotype-specific intervention in enhancing the therapeutic efficacy of TKI. A highly specific p38α inhibitor, TAK715, also significantly enhanced the imatinib- and dasatinib-mediated therapeutic efficacy, supporting the feasibility of p38α deficiency in future clinic application. Taken together, our results demonstrated that p38α is a promising target for combined therapy with BCR-ABL-targeting tyrosine kinase inhibitors for future application to increase therapeutic efficacy.

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Calcium‐dependent methylation by PRMT1 promotes erythroid differentiation through the p38α MAPK pathway

Abstract: contributed equally to this article.

Cited by 8 publications

References 50 publications

Stability of tuberous sclerosis complex 2 is controlled by methylation at R1457 and R1459

Stability of tuberous sclerosis complex 2 is controlled by methylation at R1457 and R1459

DNA or Protein Methylation-Dependent Regulation of Activator Protein-1 Function

Perturbation of p38α MAPK as a Novel Strategy to Effectively Sensitize Chronic Myeloid Leukemia Cells to Therapeutic BCR-ABL Inhibitors

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