scholarly journals Ribosomal protein S2 is a substrate for mammalian PRMT3 (protein arginine methyltransferase 3)

2005 ◽  
Vol 386 (1) ◽  
pp. 85-91 ◽  
Author(s):  
Rafal SWIERCZ ◽  
Maria D. PERSON ◽  
Mark T. BEDFORD
Keyword(s):  
Ribosomal Protein ◽  
Zinc Finger ◽  
Type I ◽  
Zinc Finger Domain ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Interacting Protein ◽  
Cell Extracts

PRMT3 (protein arginine methyltransferase 3) is one of four type I arginine methyltransferases that catalyse the formation of asymmetric dimethylarginine. PRMT3 is unique in that its N-terminus harbours a C2H2 zinc-finger domain that is proposed to confer substrate specificity. In addition, PRMT3 is the only type I enzyme that is restricted to the cytoplasm. Known in vitro substrates for PRMT3 include GST–GAR (a glutathione S-transferase fusion protein containing the glycine- and arginine-rich N-terminal region of fibrillarin), Sam68 (Src-associated substrate during mitosis 68 kDa) and PABP-N1 [poly(A)-binding protein-N1; PABP2]. Here we report the identification of an in vivo substrate for mammalian PRMT3. We found that FLAG-tagged PRMT3 can ‘pull down’ a protein with a molecular mass of 30 kDa from HeLa cell extracts. MS identified this PRMT3-interacting protein as rpS2 (ribosomal protein S2). In vitro studies showed that the zinc-finger domain of PRMT3 is necessary and sufficient for binding to rpS2. In addition, rpS2 is methylated by PRMT3 in vitro and is also methylated in cell lines. Deletion analysis of the rpS2 amino acid sequence identified a N-terminal Arg-Gly repeat as the methylation site. Furthermore, both PRMT3 and rpS2 co-sediment with free ribosomal subunits. These studies implicate PRMT3 in ribosomal function and in the regulation of protein synthesis.

scholarly journals Lambda-interacting protein, a novel protein that specifically interacts with the zinc finger domain of the atypical protein kinase C isotype lambda/iota and stimulates its kinase activity in vitro and in vivo.

1996 ◽  
Vol 16 (1) ◽  
pp. 105-114 ◽  
Author(s):  
M T Diaz-Meco ◽  
M M Municio ◽  
P Sanchez ◽  
J Lozano ◽  
J Moscat
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Zinc Finger ◽  
Zinc Finger Domain ◽  
Interacting Protein ◽  
Kinase C ◽  
Novel Protein

The members of the atypical subfamily of protein kinase C (PKC) show dramatic structural and functional differences from other PKC isotypes. Thus, in contrast to the classical or novel PKCs, they are not activated by diacylglycerol or phorbol esters. However, the atypical PKCs are the target of important lipid second messengers such as ceramide, phosphatidic acid, and 3'-phosphoinositides. The catalytic and pseudosubstrate sequences in the two atypical PKCs (lambda/iota PKC and zeta PKC) are identical but are significantly different from those of conventional or novel PKCs. It has been shown that microinjection of a peptide with the sequence of the pseudosubstrate of the atypical PKC isotypes but not of alpha PKC or epsilon PKC dramatically inhibited maturation and NF-kappa B activation in Xenopus oocytes, as well as reinitiation of DNA synthesis in quiescent mouse fibroblasts. This indicates that either or both atypical isoforms are important in cell signalling. Besides the pseudosubstrate, the major differences in the sequence between lambda/iota PKC and zeta PKC are located in the regulatory domain. Therefore, any functional divergence between the two types of atypical PKCs will presumably reside in that region. We report here the molecular characterization of lambda-interacting protein (LIP), a novel protein that specifically interacts with the zinc finger of lambda/iota PKC but not zeta PKC. We show in this paper that this interaction is detected not only in vitro but also in vivo, that LIP activates lambda/iota PKC but not zeta PKC in vitro and in vivo, and that this interaction is functionally relevant. Thus, expression of LIP leads to the transactivation of a kappa B-dependent promoter in a manner that is dependent on lambda/iota PKC. To our knowledge, this is the first report on the cloning and characterization of a protein activator of a PKC that binds to the zinc finger domain, which has so far been considered a site for binding of lipid modulators. The fact that LIP binds to lambda/iota PKC but not to the highly related zeta PKC isoform suggests that the specificity of the activation of the members of the different PKC subfamilies will most probably be accounted for by proteins like LIP rather than by lipid activators.

The Wilms tumour suppressor protein WT1 (+KTS isoform) binds alpha-actinin 1 mRNA via its zinc-finger domain

2006 ◽  
Vol 84 (5) ◽  
pp. 789-798 ◽  
Author(s):  
A.A. Morrison ◽  
J.P. Venables ◽  
G. Dellaire ◽  
M.R. Ladomery
Keyword(s):  
Zinc Finger ◽  
Nuclear Extract ◽  
Start Codon ◽  
Urogenital System ◽  
Zinc Finger Domain ◽  
Wilms Tumour ◽  
Band Shift ◽  
Mrna Targets

Mutations in WT1 are associated with developmental syndromes that affect the urogenital system and neoplasms, including Wilms tumour, acute myeloid leukemia, and breast and prostate cancers. The WT1 protein belongs to the early growth response family of zinc-finger transcription factors. Uniquely to WT1, an evolutionarily conserved alternative splice event inserts the tripeptide KTS, between zinc fingers 3 and 4. Whereas –KTS isoforms bind DNA and activate or repress transcription, +KTS isoforms bind DNA less efficiently and interact with splice factors and RNA in vitro and in vivo. Although candidate DNA targets have been found, physiological mRNA targets are yet to be defined. We examined the distribution of WT1 in ribonucleoprotein (RNP) complexes in nuclear extract prepared from M15 cells, a mouse mesonephric fetal kidney cell line. WT1 cofractionated with the splice factor PSF in large RNP particles ≥2 MDa. We also found that PSF co-immunoprecipitated with WT1, suggesting a functional interaction between these 2 multifunctional proteins. Using yeast three-hybrid library constructed from the co-immunoprecipitated RNA we found that WT1 (+KTS) binds close to or at the start codon of alpha-actinin 1 (ACTN1) mRNA. A band shift assay confirmed the ability of the WT1 zinc-finger domain (+KTS) to bind this sequence in vitro. ACTN1 is the first likely physiological mRNA target of WT1.

scholarly journals Structure, Activity and Function of the PRMT2 Protein Arginine Methyltransferase

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1263
Author(s):  
Vincent Cura ◽  
Jean Cavarelli
Keyword(s):  
Hormone Receptors ◽  
Arginine Methylation ◽  
Type I ◽  
Cellular Functions ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Cellular Processes ◽  
Src Homology ◽  
And Function

PRMT2 belongs to the protein arginine methyltransferase (PRMT) family, which catalyzes the arginine methylation of target proteins. As a type I enzyme, PRMT2 produces asymmetric dimethyl arginine and has been shown to have weak methyltransferase activity on histone substrates in vitro, suggesting that its authentic substrates have not yet been found. PRMT2 contains the canonical PRMT methylation core and a unique Src homology 3 domain. Studies have demonstrated its clear implication in many different cellular processes. PRMT2 acts as a coactivator of several nuclear hormone receptors and is known to interact with a multitude of splicing-related proteins. Furthermore, PRMT2 is aberrantly expressed in several cancer types, including breast cancer and glioblastoma. These reports highlight the crucial role played by PRMT2 and the need for a better characterization of its activity and cellular functions.

scholarly journals A Chloroacetamidine-Based Inactivator of Protein Arginine Methyltransferase 1: Design, Synthesis, and In Vitro and In Vivo Evaluation

ChemBioChem ◽  
2010 ◽  
Vol 11 (9) ◽  
pp. 1219-1223 ◽  
Author(s):  
Obiamaka Obianyo ◽  
Corey P. Causey ◽  
Tanesha C. Osborne ◽  
Justin E. Jones ◽  
Young-Ho Lee ◽  
...  
Keyword(s):  
Protein Arginine Methyltransferase ◽  
In Vivo Evaluation ◽  
Arginine Methyltransferase ◽  
Design Synthesis ◽  
Protein Arginine Methyltransferase 1 ◽  
Methyltransferase 1

scholarly journals Genetic evidence for partial redundancy between the arginine methyltransferases CARM1 and PRMT6

2020 ◽  
Vol 295 (50) ◽  
pp. 17060-17070
Author(s):  
Donghang Cheng ◽  
Guozhen Gao ◽  
Alessandra Di Lorenzo ◽  
Sandrine Jayne ◽  
Michael O. Hottiger ◽  
...  
Keyword(s):  
Direct Evidence ◽  
Type I ◽  
Gene Promoters ◽  
Double Knockout ◽  
Embryonic Fibroblasts ◽  
Arginine Methyltransferase ◽  
Fetal Size ◽  
Partial Redundancy

CARM1 is a protein arginine methyltransferase (PRMT) that acts as a coactivator in a number of transcriptional programs. CARM1 orchestrates this coactivator activity in part by depositing the H3R17me2a histone mark in the vicinity of gene promoters that it regulates. However, the gross levels of H3R17me2a in CARM1 KO mice did not significantly decrease, indicating that other PRMT(s) may compensate for this loss. We thus performed a screen of type I PRMTs, which revealed that PRMT6 can also deposit the H3R17me2a mark in vitro. CARM1 knockout mice are perinatally lethal and display a reduced fetal size, whereas PRMT6 null mice are viable, which permits the generation of double knockouts. Embryos that are null for both CARM1 and PRMT6 are noticeably smaller than CARM1 null embryos, providing in vivo evidence of redundancy. Mouse embryonic fibroblasts (MEFs) from the double knockout embryos display an absence of the H3R17me2a mark during mitosis and increased signs of DNA damage. Moreover, using the combination of CARM1 and PRMT6 inhibitors suppresses the cell proliferation of WT MEFs, suggesting a synergistic effect between CARM1 and PRMT6 inhibitions. These studies provide direct evidence that PRMT6 also deposits the H3R17me2a mark and acts redundantly with CARM1.

scholarly journals Arginine increases development of in vitro-produced porcine embryos and affects the protein arginine methyltransferase–dimethylarginine dimethylaminohydrolase–nitric oxide axis

2015 ◽  
Vol 27 (4) ◽  
pp. 655 ◽  
Author(s):  
Bethany K. Redel ◽  
Kimberly J. Tessanne ◽  
Lee D. Spate ◽  
Clifton N. Murphy ◽  
Randall S. Prather
Keyword(s):  
Nitric Oxide ◽  
Tricarboxylic Acid Cycle ◽  
Pentose Phosphate ◽  
Pyruvate Dehydrogenase Kinase ◽  
Dimethylarginine Dimethylaminohydrolase ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Cationic Amino Acid

Culture systems promote development at rates lower than the in vivo environment. Here, we evaluated the embryo’s transcriptome to determine what the embryo needs during development. A previous mRNA sequencing endeavour found upregulation of solute carrier family 7 (cationic amino acid transporter, y+ system), member 1 (SLC7A1), an arginine transporter, in in vitro- compared with in vivo-cultured embryos. In the present study, we added different concentrations of arginine to our culture medium to meet the needs of the porcine embryo. Increasing arginine from 0.12 to 1.69 mM improved the number of embryos that developed to the blastocyst stage. These blastocysts also had more total nuclei compared with controls and, specifically, more trophectoderm nuclei. Embryos cultured in 1.69 mM arginine had lower SLC7A1 levels and a higher abundance of messages involved with glycolysis (hexokinase 1, hexokinase 2 and glutamic pyruvate transaminase (alanine aminotransferase) 2) and decreased expression of genes involved with blocking the tricarboxylic acid cycle (pyruvate dehydrogenase kinase, isozyme 1) and the pentose phosphate pathway (transaldolase 1). Expression of the protein arginine methyltransferase (PRMT) genes PRMT1, PRMT3 and PRMT5 throughout development was not affected by arginine. However, the dimethylarginine dimethylaminohydrolase 1 (DDAH1) and DDAH2 message was found to be differentially regulated through development, and the DDAH2 protein was localised to the nuclei of blastocysts. Arginine has a positive effect on preimplantation development and may be affecting the nitric oxide–DDAH–PRMT axis.

Peculiarities of the course of type I allergic reactions in patients with blood diseases

2020 ◽  
pp. 40-50
Author(s):  
A. Nikitina
Keyword(s):  
Search Engines ◽  
Anaphylactic Shock ◽  
Type I ◽  
Allergic Reactions ◽  
Common Cause ◽  
Blood Diseases ◽  
Treatment Regimens ◽  
Modern Methods

Analysis of literature data presented in search engines — Elibrary, PubMed, Cochrane — concerning the risk of developing type I allergic reactions in patients with blood diseases is presented. It is shown that the most common cause of type I allergic reactions is drugs included in the treatment regimens of this category of patients. The article presents statistics on the increase in the number of drug allergies leading to cases of anaphylactic shock in patients with blood diseases. Modern methods for the diagnosis of type I allergic reactions in vivo and in vitro are considered.

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