Naturally occurring cancer-associated mutations disrupt oligomerization and activity of protein arginine methyltransferase 1 (PRMT1)

Price, Owen M.; Thakur, Abhishek; Ortolano, Ariana; Towne, Arianna; Velez, Caroline; Acevedo, Orlando; Hevel, Joan M.

doi:10.1016/j.jbc.2021.101336

“…Moreover, how TIPE1 regulates PRMT1-medicated total STAT3 protein expression need to be further elucidated. Arginine methylation by PRMT1 participates in several cellular processes, including DNA damage repair, transcriptional regulation, apoptosis, and cell proliferation [ 50 ]. Previous study has revealed that PRMT1 regulates ATF4 protein stability through methylation of R239, and plays a protective role against ER stress-mediated cell death in the myocardium [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

TIPE1 inhibits osteosarcoma tumorigenesis and progression by regulating PRMT1 mediated STAT3 arginine methylation

Yang

¹

,

Zhang

²

,

Liu

³

et al. 2022

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Osteosarcoma (OS), the most common primary malignancy of the bone, has a poor prognosis due to its high mortality rate and high potential for metastasis. Thus, it is urgently necessary to explore functional molecular targets of therapeutic strategies for osteosarcoma. Here, we reported that TIPE1 expression was decreased in osteosarcoma tissues compared to normal and adjacent nontumor tissues, and its expression was negatively related to tumor stage and tumor size. Functional assays showed that TIPE1 inhibited osteosarcoma carcinogenesis and metastatic potential both in vivo and in vitro. Furthermore, we investigated that the STAT3 signaling pathway was significantly downregulated after TIPE1 overexpression. Mechanistically, TIPE1 bind to the catalytic domain of PRMT1, which deposits an asymmetric dimethylarginine (ADMA) mark on histone/non-histone proteins, and thus inhibited PRMT1 mediated STAT3 methylation at arginine (R) residue 688. This abolished modification decreased STAT3 transactivation and expression, by which subsequently suppressed osteosarcoma malignancy. Taken together, these data showed that TIPE1 inhibits the malignant transformation of osteosarcoma through PRMT1-mediated STAT3 arginine methylation and ultimately decreases the development and metastasis of osteosarcoma. TIPE1 might be a potential molecular therapeutic target and an early biomarker for osteosarcoma diagnosis.

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“…Cluster analysis is a method of determining a population ensemble during MD simulation by grouping similar conformations together over the trajectory. In this study, the cpptraj “average-linkage” algorithm was used, 33 , 36 where for the distance metric, RMSD of atoms with a sieve of 10 was applied.…”

Section: Methodsmentioning

confidence: 99%

SELEX based aptamers with diagnostic and entry inhibitor therapeutic potential for SARS-CoV-2

Halder,

Thakur,

Keshry

et al. 2023

Sci Rep

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Frequent mutation and variable immunological protection against vaccination is a common feature for COVID-19 pandemic. Early detection and confinement remain key to controlling further spread of infection. In response, we have developed an aptamer-based system that possesses both diagnostic and therapeutic potential towards the virus. A random aptamer library (~ 1017 molecules) was screened using systematic evolution of ligands by exponential enrichment (SELEX) and aptamer R was identified as a potent binder for the SARS-CoV-2 spike receptor binding domain (RBD) using in vitro binding assay. Using a pseudotyped viral entry assay we have shown that aptamer R specifically inhibited the entry of a SARS-CoV-2 pseudotyped virus in HEK293T-ACE2 cells but did not inhibit the entry of a Vesicular Stomatitis Virus (VSV) glycoprotein (G) pseudotyped virus, hence establishing its specificity towards SARS-CoV-2 spike protein. The antiviral potential of aptamers R and J (same central sequence as R but lacking flanked primer regions) was tested and showed 95.4% and 82.5% inhibition, respectively, against the SARS-CoV-2 virus. Finally, intermolecular interactions between the aptamers and the RBD domain were analyzed using in silico docking and molecular dynamics simulations that provided additional insight into the binding and inhibitory action of aptamers R and J.

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“…Cluster analysis is a method of determining a population ensemble during MD simulation by grouping similar conformations together over the trajectory. In this study, the cpptraj "average-linkage" algorithm was used, 31,34 where for the distance metric, RMSD of atoms with a sieve of 10 was applied.…”

Section: Cluster Analysismentioning

confidence: 99%

SELEX based aptamers with diagnostic and entry inhibitor therapeutic potential for SARS-CoV-2

Halder¹,

Thakur

²

,

Keshry

³

et al. 2023

Preprint

Self Cite

0

View full text Add to dashboard Cite

Frequent mutation and variable immunological protection against vaccination is a common feature for COVID-19 pandemic. Early detection and confinement remain key to controlling further spread of infection. In response, we have developed an aptamer-based system that possesses both diagnostic and therapeutic potential towards the virus. A random aptamer library (~ 1017 molecules) was screened using systematic evolution of ligands by exponential enrichment (SELEX) and aptamer R was identified as a potent binder for the SARS-CoV-2 spike receptor binding domain (RBD) using in vitro binding assay. Using a pseudotyped viral entry assay we have shown that aptamer R specifically inhibited the entry of a SARS-CoV-2 pseudotyped virus in HEK293T-ACE2 cells but did not inhibit the entry of a Vesicular Stomatitis Virus (VSV) glycoprotein (G) pseudotyped virus, hence establishing its specificity towards SARS-CoV-2 spike protein. The antiviral potential of aptamers R and J (same central sequence as R but lacking flanked primer regions) was tested and showed 95.4% and 82.5% inhibition, respectively, against the SARS-CoV-2 virus. Finally, intermolecular interactions between the aptamers and the RBD domain were analyzed using in silico docking and molecular dynamics simulations that provided additional insight into the binding and inhibitory action of aptamers R and J.

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Naturally occurring cancer-associated mutations disrupt oligomerization and activity of protein arginine methyltransferase 1 (PRMT1)

Cited by 14 publications

References 109 publications

TIPE1 inhibits osteosarcoma tumorigenesis and progression by regulating PRMT1 mediated STAT3 arginine methylation

TIPE1 inhibits osteosarcoma tumorigenesis and progression by regulating PRMT1 mediated STAT3 arginine methylation

SELEX based aptamers with diagnostic and entry inhibitor therapeutic potential for SARS-CoV-2

SELEX based aptamers with diagnostic and entry inhibitor therapeutic potential for SARS-CoV-2

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