An unexpected journey: Lysine methylation across the proteome

Moore, Kaitlyn E.; Gozani, Or

doi:10.1016/j.bbagrm.2014.02.008

Cited by 87 publications

(66 citation statements)

References 140 publications

(243 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Emerging evidence suggest that histone methyltransferases and demethylases use both histones and nonhistone proteins as substrates, exerting functional roles in a multitude of biological processes (40)(41)(42)(43)(44). HSP70 proteins have been known to be methylated on both arginine and lysine residues for decades, but the exact methylation sites, their methyltransferases and demethylases, and the biological functions of these modifications remain incompletely understood (29).…”

Section: Discussionmentioning

confidence: 99%

Arginine methylation of HSP70 regulates retinoid acid-mediated RARβ2 gene activation

Gao

Xiao

Peng

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Although "histone" methyltransferases and demethylases are well established to regulate transcriptional programs and to use nonhistone proteins as substrates, their possible roles in regulation of heat-shock proteins in the nucleus have not been investigated. Here, we report that a highly conserved arginine residue, R469, in HSP70 (heat-shock protein of 70 kDa) proteins, an evolutionarily conserved protein family of ATP-dependent molecular chaperone, was monomethylated (me1), at least partially, by coactivatorassociated arginine methyltransferase 1/protein arginine methyltransferase 4 (CARM1/PRMT4) and demethylated by jumonjidomain-containing 6 (JMJD6), both in vitro and in cultured cells. Functional studies revealed that HSP70 could directly regulate retinoid acid (RA)-induced retinoid acid receptor β2 (RARβ2) gene transcription through its binding to chromatin, with R469me1 being essential in this process. HSP70's function in gene transcriptional regulation appears to be distinct from its protein chaperon activity. R469me1 was shown to mediate the interaction between HSP70 and TFIIH, which involves in RNA polymerase II phosphorylation and thus transcriptional initiation. Our findings expand the repertoire of nonhistone substrates targeted by PRMT4 and JMJD6, and reveal a new function of HSP70 proteins in gene transcription at the chromatin level aside from its classic role in protein folding and quality control.heat-shock proteins | arginine methylation | gene transcription

show abstract

Section: Discussionmentioning

confidence: 99%

Arginine methylation of HSP70 regulates retinoid acid-mediated RARβ2 gene activation

Gao

Xiao

Peng

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Protein methylation occurs in all three domains of life (1)(2)(3)(4)(5)(6). In Eukarya, methylation of lysine and arginine residues in histones is involved in the control of gene expression (7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

aKMT Catalyzes Extensive Protein Lysine Methylation in the Hyperthermophilic Archaeon Sulfolobus islandicus but is Dispensable for the Growth of the Organism

Chu

Zhu

Chen

et al. 2016

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Protein methylation is believed to occur extensively in creanarchaea. Recently, aKMT, a highly conserved crenarchaeal protein lysine methyltransferase, was identified and shown to exhibit broad substrate specificity in vitro. Here, we have constructed an aKMT deletion mutant of the hyperthermophilic crenarchaeon Sulfolobus islandicus. The mutant was viable but showed a moderately slower growth rate than the parental strain under nonoptimal growth conditions. Consistent with the moderate effect of the lack of aKMT on the growth of the cell, expression of a small number of genes, which encode putative functions in substrate transportation, energy metabolism, transcriptional regulation, stress response proteins, etc, was differentially regulated by more than twofold in the mutant strain, as compared with that in the parental strain. Analysis of the methylation of total cellular protein by mass spectrometry revealed that methylated proteins accounted for ϳ2/3 (1,158/1,751) and ϳ1/3 (591/ 1,757) of the identified proteins in the parental and the mutant strains, respectively, indicating that there is extensive protein methylation in S. islandicus and that aKMT is a major protein methyltransferase in this organism. No significant sequence preference was detected at the sites of methylation by aKMT. Methylated lysine residues, when visible in the structure, are all located on the surface of the proteins. The crystal structure of aKMT in complex with S-adenosyl-L-methionine (SAM) or S-adenosyl homocysteine (SAH) reveals that the protein consists of four ␣ helices and seven ␤ sheets, lacking a substrate recognition domain found in PrmA, a bacterial homolog of aKMT, in agreement with the broad substrate specificity of aKMT. Our results suggest that aKMT may serve a role in maintaining the methylation status of cellular proteins required for the efficient growth of the organism under certain non-optimal conditions. Molecular & Cellular

show abstract

“…For example, me1 of histone H3 at lysine 4 will be referred to H3K4me1. In humans, the canonical lysine methylation sites on the core histones are H3K4, H3K9, H3K27, H3K36, H3K79, and H4K20 (10). Here, to highlight the functional complexity that can be added to the proteome via lysine methylation, we focus on the signaling pathways and functions associated with methylation of a single residue, H4K20, as a model chromatin and clinically important mark that regulates diverse biological processes ranging from the DNA damage response and DNA replication to gene expression and silencing.…”

mentioning

confidence: 99%

Histone H4 Lysine 20 (H4K20) Methylation, Expanding the Signaling Potential of the Proteome One Methyl Moiety at a Time

Nuland

Gozani

2016

Molecular & Cellular Proteomics

Self Cite

View full text Add to dashboard Cite

Covalent post-translational modifications (PTMs) of proteins can regulate the structural and functional state of a protein in the absence of primary changes in the underlying sequence. Common PTMs include phosphorylation, acetylation, and methylation. Histone proteins are critical regulators of the genome and are subject to a highly abundant and diverse array of PTMs. To highlight the functional complexity added to the proteome by lysine methylation signaling, here we will focus on lysine methylation of histone proteins, an important modification in the regulation of chromatin and epigenetic processes. We review the signaling pathways and functions associated with a single residue, H4K20, as a model chromatin and clinically important mark that regulates biological processes ranging from the DNA damage response and DNA replication to gene expression and silencing. Molecular

show abstract

An unexpected journey: Lysine methylation across the proteome

Cited by 87 publications

References 140 publications

Arginine methylation of HSP70 regulates retinoid acid-mediated RARβ2 gene activation

Arginine methylation of HSP70 regulates retinoid acid-mediated RARβ2 gene activation

aKMT Catalyzes Extensive Protein Lysine Methylation in the Hyperthermophilic Archaeon Sulfolobus islandicus but is Dispensable for the Growth of the Organism

Histone H4 Lysine 20 (H4K20) Methylation, Expanding the Signaling Potential of the Proteome One Methyl Moiety at a Time

Contact Info

Product

Resources

About