A Mass Spectrometric Study on the in Vitro Methylation of HMGA1a and HMGA1b Proteins by PRMTs:  Methylation Specificity, the Effect of Binding to AT-Rich Duplex DNA, and the Effect of C-Terminal Phosphorylation

Yan, Zaoxue; Webb, Kristofor; Perna, Avi; Zhang, Qingchun; Clarke, Steven; Wang, Yinsheng

doi:10.1021/bi6024897

Cited by 40 publications

(35 citation statements)

References 56 publications

(137 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Arginine methylation in this region thus probably plays an important role in HMGA functions. All findings on methylation of the HMGA1 proteins on different Arg residues were very recently confirmed and extended by Zou et al (67).…”

Section: Long-range Chromatin Interactionssupporting

confidence: 69%

The HMGA proteins: A myriad of functions (Review)

Cleynen

Ven²

2008

Int J Oncol

214

243

View full text Add to dashboard Cite

Abstract. The 'high mobility group' HMGA protein family consists of four members: HMGA1a, HMGA1b and HMGA1c, which result from translation of alternative spliced forms of one gene and HMGA2, which is encoded for by another gene. HMGA proteins are characterized by three DNA-binding domains, called AT-hooks, and an acidic carboxy-terminal tail. HMGA proteins are architectural transcription factors that both positively and negatively regulate the transcription of a variety of genes. They do not display direct transcriptional activation capacity, but regulate gene expression by changing the DNA conformation by binding to AT-rich regions in the DNA and/or direct interaction with several transcription factors. In this way, they influence a diverse array of normal biological processes including cell growth, proliferation, differentiation and death. Both HMGA1 and HMGA2 are hardly detectable in normal adult tissue but are abundantly and ubiquitously expressed during embryonic development. In malignant epithelial tumors as well as in leukemia, however, expression of HMGA1 is again strongly elevated to embryonic levels thus leading to ectopic expression of (fetal) target genes. HMGA2 overexpression also has a causal role in inducing neoplasia. Besides overexpression of full length HMGA proteins in different tumors, the HMGA genes are often involved in chromosomal rearrangements. Such translocations are mostly detected in benign tumors of mesenchymal origin and are believed to be one of the most common chromosomal rearrangements in human neoplasia. To provide clarity in the abundance of articles on this topic, this review gives a general overview of the nuclear functions and regulation of the HMGA genes and corresponding proteins.

show abstract

Section: Long-range Chromatin Interactionssupporting

confidence: 69%

The HMGA proteins: A myriad of functions (Review)

Cleynen

Ven²

2008

Int J Oncol

214

243

View full text Add to dashboard Cite

show abstract

“…In this context, Sgarra et al [88] reported that the methylation occurs on Arg-25 in the first AT-hook, and later we found that the same site, i.e., Arg-25, can be both mono-and dimethylated in PC-3 human prostate cancer cells. In addition, both isoforms of dimethylation, i.e., symmetric and asymmetric dimethylation, were detected [90]; the asymmetric and symmetric dimethylarginines were assessed by MS/MS based on characteristic neutral losses from the side chains of the modified arginines [90][91][92].…”

Section: Ptms Of Hmga Proteinsmentioning

confidence: 99%

High mobility group proteins and their post-translational modifications

Zhang

Wang

2008

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

Self Cite

View full text Add to dashboard Cite

The high mobility group (HMG) proteins, including HMGA, HMGB and HMGN, are abundant and ubiquitous nuclear proteins that bind to DNA, nucleosome and other multi-protein complexes in a dynamic and reversible fashion to regulate DNA processing in the context of chromatin. All HMG proteins, like histone proteins, are subjected to extensive post-translational modifications (PTMs), such as lysine acetylation, arginine/lysine methylation and serine/threonine phosphorylation, to modulate their interactions with DNA and other proteins. There is a growing appreciation for the complex relationship between the PTMs of HMG proteins and their diverse biological activities. Here, we reviewed the identified covalent modifications of HMG proteins, and highlighted how these PTMs affect the functions of HMG proteins in a variety of cellular processes.

show abstract

“…PRMT6 exhibits a relatively narrow substrate specificity, with the currently known substrates being HMG1A (66,87,106), histone subunits (32,37,38), DNA polymerase beta (20), and several components of the HIV virus (10, 39, 40) as well as PRMT6 itself (28). The human enzyme is reported to display an exclusively nuclear localization pattern (28), consistent with its known roles in…”

mentioning

confidence: 99%

TbPRMT6 Is a Type I Protein Arginine Methyltransferase That Contributes to Cytokinesis in Trypanosoma brucei

et al. 2010

View full text Add to dashboard Cite

Arginine methylation is a widespread posttranslational modification of proteins catalyzed by a family of protein arginine methyltransferases (PRMTs). In Saccharomyces cerevisiae and mammals, this modification affects multiple cellular processes, such as chromatin remodeling leading to transcriptional regulation, RNA processing, DNA repair, and cell signaling. The protozoan parasite Trypanosoma brucei possesses five putative PRMTs in its genome. This is a large number of PRMTs relative to other unicellular eukaryotes, suggesting an important role for arginine methylation in trypanosomes. Here, we present the in vitro and in vivo characterization of a T. brucei enzyme homologous to human PRMT6, which we term TbPRMT6. Like human PRMT6, TbPRMT6 is a type I PRMT, catalyzing the production of monomethylarginine and asymmetric dimethylarginine residues. In in vitro methylation assays, TbPRMT6 utilizes bovine histones as a substrate, but it does not methylate several T. brucei glycine/arginine-rich proteins. As such, it exhibits a relatively narrow substrate specificity compared to other T. brucei PRMTs. Knockdown of TbPRMT6 in both procyclic form and bloodstream form T. brucei leads to a modest but reproducible effect on parasite growth in culture. Moreover, upon TbPRMT6 depletion, both PF and BF exhibit aberrant morphologies indicating defects in cell division, and these defects differ in the two life cycle stages. Mass spectrometry of TbPRMT6-associated proteins reveals histones, components of the nuclear pore complex, and flagellar proteins that may represent TbPRMT6 substrates contributing to the observed growth and morphological defects.Posttranslational methylation of proteins on arginine residues has multiple roles in a wide array of cellular functions, such as chromatin remodeling leading to transcription activation or repression, RNA processing, DNA repair, and various forms of cell signaling (5,6,8,9,52,70,98). The process of arginine methylation involves the transfer of methyl groups from S-adenosyl-methionine (AdoMet) to arginine residues of proteins and is catalyzed by a group of enzymes known as protein arginine methyltransferases (PRMTs). PRMTs themselves are further divided into four classes, depending on the type of methylated arginine generated. The largest PRMT class comprises the type I enzymes, as characterized by the first discovered PRMT, PRMT1. Type I PRMTs initially catalyze the formation of monomethylated arginine (MMA) on the terminal -nitrogen, followed by addition of a second methyl group on the same -nitrogen, which yields asymmetric dimethylarginine (ADMA). The type II PRMTs are a smaller group, presently consisting only of PRMT5 and its homologues. These enzymes also catalyze the synthesis of MMA on the terminal -nitrogen, but in contrast to the type I enzymes, type II PRMTs add a second methyl group to the adjacent terminal -nitrogen, resulting in symmetric dimethylarginine (SDMA). Almost all known eukaryotic cells possess at least one type I PRMT and one type II PRMT in the form of PRM...

show abstract

A Mass Spectrometric Study on the in Vitro Methylation of HMGA1a and HMGA1b Proteins by PRMTs: Methylation Specificity, the Effect of Binding to AT-Rich Duplex DNA, and the Effect of C-Terminal Phosphorylation

Cited by 40 publications

References 56 publications

The HMGA proteins: A myriad of functions (Review)

The HMGA proteins: A myriad of functions (Review)

High mobility group proteins and their post-translational modifications

TbPRMT6 Is a Type I Protein Arginine Methyltransferase That Contributes to Cytokinesis in Trypanosoma brucei

Contact Info

Product

Resources

About