更新于：2024-11-01

NTMT1

更新于：2024-11-01

基本信息

别名

AD-003、Alpha N-terminal protein methyltransferase 1A、C9orf32

+ [11]

简介

Distributive alpha-N-methyltransferase that methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Gly/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. Specifically catalyzes mono-, di- or tri-methylation of the exposed alpha-amino group of the Ala, Gly or Ser residue in the [Ala/Gly/Ser]-Pro-Lys motif and mono- or di-methylation of Pro in the Pro-Pro-Lys motif. Some of the substrates may be primed by NTMT2-mediated monomethylation (PubMed:24090352). Catalyzes the trimethylation of the N-terminal Gly in CENPA (after removal of Met-1). Responsible for the N-terminal methylation of KLHL31, MYL2, MYL3, RB1, RCC1, RPL23A and SET. Required during mitosis for normal bipolar spindle formation and chromosome segregation via its action on RCC1.

关联

项与 NTMT1 相关的药物

BM30

靶点

NTMT1 x NTMT2

作用机制

NTMT1 inhibitors [+1]

在研机构

Virginia Commonwealth University

原研机构

Virginia Commonwealth University

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

DC432

靶点

NTMT1 x NTMT2

作用机制

NTMT1 inhibitors [+1]

在研机构

Virginia Commonwealth University

原研机构

Virginia Commonwealth University

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

DC541

靶点

NTMT1

作用机制

NTMT1 inhibitors

在研机构

Purdue University

原研机构

Purdue University

在研适应症-

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 NTMT1 相关的临床结果

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100 项与 NTMT1 相关的转化医学

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0 项与 NTMT1 相关的专利（医药）

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项与 NTMT1 相关的文献（医药）

2024-10-04·Journal of Proteome Research

Characterizations of Protein Arginine Deiminase 1 as a Substrate of NTMT1: Implications of Nα-Methylation in Protein Stability and Interaction

Article

作者: He, Ming ; Wang, Yinsheng ; Huang, Rong ; Deng, Youchao ; Meng, Ying ; Li, Zhouxian ; Zhang, Quanqing

α-N-Methylation (Nα-methylation), catalyzed by protein N-terminal methyltransferases (NTMTs), constitutes a crucial post-translational modification involving the transfer of a methyl group from S-adenosyl-l-methionine (SAM) to the Nα-terminal amino group of substrate proteins. NTMT1/2 are known to methylate canonical Nα sequences, such as X-P-K/R. With over 300 potential human protein substrates, only a small fraction has been validated, and even less is known about the functions of Nα-methylation. This study delves into the characterizations of protein arginine deiminase 1 (PAD1) as a substrate of NTMT1. By employing biochemical and cellular assays, we demonstrated NTMT1-mediated Nα-methylation of PAD1, leading to an increase in protein half-life and the modulation of protein-protein interactions in HEK293T cells. The methylation of PAD1 appears nonessential to its enzymatic activity or cellular localization. Proteomic studies revealed differential protein interactions between unmethylated and Nα-methylated PAD1, suggesting a regulatory role for Nα-methylation in modulating PAD1's protein-protein interactions. These findings shed light on the intricate molecular mechanisms governing PAD1 function and expand our knowledge of Nα-methylation in regulating protein function.

2024-01-01·Journal of Biochemical and Molecular Toxicology

Pan‐cancer analysis reveals the pro‐oncogenic role of N6‐methyladenosine (m6A)‐regulated NTMT1 in head and neck squamous cell carcinoma

Article

作者: Zhao, Chunhong ; Li, Yujie ; Yu, Min

AbstractHead and neck squamous cell carcinoma (HNSC) is a common and fatal tumor with a bleak prognosis, posing a significant threat to human health. N6‐methyladenosine (m6A) modification regulates tumor progression by modulating gene expression post‐transcriptionally. Nevertheless, the specific function of m6A‐modified tumor drivers in HNSC remains largely uncharted. In this study, we revealed the pro‐oncogenic role of m6A‐regulated NTMT1 in HNSC through comprehensive pan‐cancer analysis and experimental validation. By scrutinizing the prognostic and expression profiles of NTMT1 across over 30 cancer types, we observed a significant association between NTMT1 and patient overall survival in ACC, HNSC, LAML, LGG, KIRC, and STAD. Moreover, we find a close correlation between NTMT1 and disease‐free survival in ACC, HNSC, LUSC, UVM, KIRC, and STAD. NTMT1 exhibited dysregulation in 15 cancers, including CESC, CHOL, COAD, DLBC, GBM, HNSC, LGG, LIHC, PAAD, READ, SKCM, THYM, UCS, LAML, and TGCT. Integrated data underscored the critical involvement of NTMT1 in HNSC. Furthermore, the expression of NTMT1 was closely associated with tumor stage and immune infiltration in HNSC. Functionally, NTMT1 deficiency was demonstrated to significantly impede cell proliferation and cell‐cycle progression in HNSC. Mechanistically, METTL3 was elucidated to mediate the epigenetic upregulation of NTMT1 in HNSC in an m6A‐dependent manner, and the overexpression of METTL3 was shown to alleviate the inhibitory impact of downregulated NTMT1 on HNSC proliferation. In conclusion, our findings enhance our understanding of NTMT1's role across various cancer types and offer a rationale for clinically targeting NTMT1 as a therapeutic approach for HNSC.

2023-12-06·The Journal of Neuroscience

Spinal-Specific Super Enhancer in Neuropathic Pain

Article

作者: Tao, Yang ; Zhang, Ming ; Yang, Li ; Wang, Hong-Jun ; Wang, Qi-Hui ; Li, Si-Yuan ; Sun, Run-Hang ; Hao, Ling-Yun ; Liu, Ya ; Cao, Jun-Li ; Li, Xiao-Tong ; Xu, Heng-Jun ; Pan, Zhiqiang

Dysfunctional gene expression in nociceptive pathways plays a critical role in the development and maintenance of neuropathic pain. Super enhancers (SEs), composed of a large cluster of transcriptional enhancers, are emerging as new players in the regulation of gene expression. However, whether SEs participate in nociceptive responses remains unknown. Here, we report a spinal-specific SE (SS-SE) that regulates chronic constriction injury (CCI)-induced neuropathic pain by drivingNtmt1andPrrx2transcription in dorsal horn neurons. Peripheral nerve injury significantly enhanced the activity of SS-SE and increased the expression of NTMT1 and PRRX2 in the dorsal horn of male mice in a bromodomain-containing protein 4 (BRD4)-dependent manner. Both intrathecal administration of a pharmacological BRD4 inhibitor JQ1 and CRISPR-Cas9-mediated SE deletion abolished the increased NTMT1 and PRRX2 in CCI mice and attenuated their nociceptive hypersensitivities. Furthermore, knocking downNtmt1orPrrx2with siRNA suppressed the injury-induced elevation of phosphorylated extracellular-signal-regulated kinase (p-ERK) and glial fibrillary acidic protein (GFAP) expression in the dorsal horn and alleviated neuropathic pain behaviors. Mimicking the increase in spinalNtmt1orPrrx2in naive mice increased p-ERK and GFAP expression and led to the genesis of neuropathic pain-like behavior. These results redefine our understanding of the regulation of pain-related genes and demonstrate that BRD4-driven increases in SS-SE activity is responsible for the genesis of neuropathic pain through the governance of NTMT1 and PRRX2 expression in dorsal horn neurons. Our findings highlight the therapeutic potential of BRD4 inhibitors for the treatment of neuropathic pain.SIGNIFICANCE STATEMENTSEs drive gene expression by recruiting master transcription factors, cofactors, and RNA polymerase, but their role in the development of neuropathic pain remains unknown. Here, we report that the activity of an SS-SE, located upstream of the genesNtmt1andPrrx2, was elevated in the dorsal horn of mice with neuropathic pain. SS-SE contributes to the genesis of neuropathic pain by driving expression ofNtmt1andPrrx2. Both inhibition of SS-SE with a pharmacological BRD4 inhibitor and genetic deletion of SS-SE attenuated pain hypersensitivities. This study suggests an effective and novel therapeutic strategy for neuropathic pain.