<scp>MST2</scp> methylation by <scp>PRMT5</scp> inhibits Hippo signaling and promotes pancreatic cancer progression

Sun, Yan; Jin, Xin; Meng, Junpeng; Guo, Feng; Chen, Taoyu; Zhao, Xiaoyan; Wu, Heshui; Ren, Dianyun

doi:10.15252/embj.2023114558

Cited by 5 publications

(3 citation statements)

References 49 publications

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“…This may be explained by the fact that PRMT5 bounds to the NT and, to a lesser extent, the DBD and LBD domain of Nur77, hence the mutation R346 alone is not able to abolish the interaction between Nur77 and PRMT5. Although the detailed mechanism of AKT signaling activation in PRMT5 deficient EnSC has not been clarified here, a recent study reported that PRMT5 promotes AKT activation by catalyzing symmetric dimethylation of AKT1 at R391 in MCF7 cells (54). However, we did not observe the expression of AKT-sDMA in proliferative or differentiated EnSC (Figure 7A).…”

Section: Discussioncontrasting

confidence: 57%

PRMT5 deficiency disturbs Nur77 methylation to inhibit endometrial stromal cell differentiation in recurrent implantation failure

Cao,

Wang,

Liu

et al. 2024

Preprint

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Various posttranslational modifications (PTMs) have been implicated in endometrial stromal cell (EnSC) differentiation, but the potential role of PTM crosstalk has not been identified. Here, we report that protein arginine methyltransferase 5 (PRMT5) is indispensable for human endometrial decidualization, functioning as a key regulator of decidualization defect in recurrent implantation failure (RIF) patients. Uterine-selective deletion ofPrmt5led to defective embryo implantation in mice due to impaired EnSC decidualization. Mechanistically, we find that PRMT5 catalyzes symmetric dimethylation of orphan nuclear receptor Nur77 at arginine 346, which in turn promotes Nur77 nuclear localization and increases its transcriptional activity in EnSC. Moreover, we demonstrate that PRMT5-mediated Nur77 methylation antagonizes AKT-induced phosphorylation of Nur77 at serine 351 in the transition from proliferation to differentiation of EnSC and disruption of the balance between methylation and phosphorylation of Nur77 is essentially involved in the endometrium of RIF patients. Furthermore, by modulating the methylation-phosphorylation of Nur77 and its transcriptional activity, we rescued impaired decidualization in RIF, further highlighting the critical role of the PRMT5/AKT/Nur77 complex in uterine receptivity to embryo implantation.

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Section: Discussioncontrasting

confidence: 57%

PRMT5 deficiency disturbs Nur77 methylation to inhibit endometrial stromal cell differentiation in recurrent implantation failure

Cao,

Wang,

Liu

et al. 2024

Preprint

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“…KDM5B can also be involved in the immune escape mechanism of melanoma in combination with HMT SETDB1 [ 142 ]. PRMT5 is elevated in various hematologic malignancies and solid cancers and is responsible for maintaining muscle development and regeneration under normal physiology [ 143 – 146 ]. However, PRMT5 has more than just a promoting effect in cancer, and it has been confirmed that PRMT5 has a tumor-suppressive effect in clear cell renal cell carcinoma [ 147 ].…”

Section: Types Of Chromatin Modifiersmentioning

confidence: 99%

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Nie,

Song,

Huang

et al. 2024

Mol Biomed

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The field of transcriptional regulation has revealed the vital role of chromatin modifiers in human diseases from the beginning of functional exploration to the process of participating in many types of disease regulatory mechanisms. Chromatin modifiers are a class of enzymes that can catalyze the chemical conversion of pyrimidine residues or amino acid residues, including histone modifiers, DNA methyltransferases, and chromatin remodeling complexes. Chromatin modifiers assist in the formation of transcriptional regulatory circuits between transcription factors, enhancers, and promoters by regulating chromatin accessibility and the ability of transcription factors to acquire DNA. This is achieved by recruiting associated proteins and RNA polymerases. They modify the physical contact between cis-regulatory factor elements, transcription factors, and chromatin DNA to influence transcriptional regulatory processes. Then, abnormal chromatin perturbations can impair the homeostasis of organs, tissues, and cells, leading to diseases. The review offers a comprehensive elucidation on the function and regulatory mechanism of chromatin modifiers, thereby highlighting their indispensability in the development of diseases. Furthermore, this underscores the potential of chromatin modifiers as biomarkers, which may enable early disease diagnosis. With the aid of this paper, a deeper understanding of the role of chromatin modifiers in the pathogenesis of diseases can be gained, which could help in devising effective diagnostic and therapeutic interventions.

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“…In addition to the abnormal expression of PRMT family members, the regulation of their activities and functions may also have important effects on tumorigenesis and progression. It was found that some members of the PRMT family were found to interact with tumor-associated proteins, regulate their methylation status, and further affect the function of these proteins [17,18]. This implies that it is possible to develop therapeutic strategies for targeting tumors by modulating the activity and function of PRMT family members.…”

Section: Introductionmentioning

confidence: 99%

Identification of protein methyltransferases 5 associated with ferroptosis and immune cell infiltration of head and neck squamous cell carcinoma

Zhang,

Liu,

Wang

et al. 2024

Aging

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Head and neck tumors are malignant tumors that appear in the head and neck. Although much progress has been made in the treatment of head and neck tumors, many challenges remain. The prognosis of some advanced cases remains poor and survival and quality of life after treatment face certain limitations. Therefore, further research into the pathogenesis and treatment options for head and neck tumors is important in order to improve the prognosis and quality of life of patients. The Protein Arginine Methyltransferase (PRMT) family is a class of enzymes that are responsible for adding methyl groups to arginine residues in proteins. PRMT family members play important roles in regulating many cellular processes, such as transcriptional regulation, signaling, and cell cycle regulation. Recent studies have shown that the PRMT family also plays an important function in tumorigenesis and development. Here, we found that PRMT family members are significantly overexpressed in head and neck tumors and that PRMT5 may serve as an independent prognostic factor in head and neck tumors. We found that PRMT5-regulated differential genes were significantly enriched in tumorassociated signaling pathways such as IL-17 and p53. And we also found that the expression of PRMT5 in head and neck tumors was significantly correlated with immune cell infiltration, m6A as well as the expression of ferroptosis-related genes, and drug sensitivity. These results suggest that PRMT may play an important role in the development of head and neck tumors.

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MST2 methylation by PRMT5 inhibits Hippo signaling and promotes pancreatic cancer progression

Cited by 5 publications

References 49 publications

PRMT5 deficiency disturbs Nur77 methylation to inhibit endometrial stromal cell differentiation in recurrent implantation failure

PRMT5 deficiency disturbs Nur77 methylation to inhibit endometrial stromal cell differentiation in recurrent implantation failure

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Identification of protein methyltransferases 5 associated with ferroptosis and immune cell infiltration of head and neck squamous cell carcinoma

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