In Vivo Acetylation of HMG1 Protein Enhances Its Binding Affinity to Distorted DNA Structures

Ugrinova, Iva; Pasheva, Evdokia; Armengaud, Jean; Pashev, Iliya G.

doi:10.1021/bi0113364

Cited by 59 publications

(52 citation statements)

References 54 publications

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“…However, acetylation of a single lysine has been shown to alter binding affinity of proteins; for example, binding of highmobility-group 1 (HMG1) protein to DNA (Ugrinova et al, 2001) and binding of nuclear steroid hormone receptors to the ACTR coactivator (Chen et al, 1999). Analogously, monoacetylation of histone H4 is sufficient to alter recognition by transcriptional machinery (Girardot et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions

Tran

Marmo

Salam

et al. 2007

Journal of Cell Science

245

215

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Genetic or pharmacological alteration of the activity of the histone deacetylase 6 (HDAC6) induces a parallel alteration in cell migration. Using tubacin to block deacetylation of α-tubulin, and not other HDAC6 substrates, yielded a motility reduction equivalent to agents that block all NAD-independent HDACs. Accordingly, we investigated how the failure to deacetylate tubulin contributes to decreased motility in HDAC6-inhibited cells. Testing the hypothesis that motility is reduced because cellular adhesion is altered, we found that inhibiting HDAC6 activity towards tubulin rapidly increased total adhesion area. Next, we investigated the mechanism of the adhesion area increase. Formation of adhesions proceeded normally and cell spreading was more rapid in the absence of active HDAC6; however, photobleaching assays and adhesion breakdown showed that adhesion turnover was slower. To test the role of hyperacetylated tubulin in altering adhesion turnover, we measured microtubule dynamics in HDAC6-inhibited cells because dynamic microtubules are required to target adhesions for turnover. HDAC6 inhibition yielded a decrease in microtubule dynamics that was sufficient to decrease focal adhesion turnover. Thus, our results suggest a scenario in which the decreased dynamics of hyperacetylated microtubules in HDAC6-inhibited cells compromises their capacity to mediate the focal adhesion dynamics required for rapid cell migration.

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Section: Discussionmentioning

confidence: 99%

HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions

Tran

Marmo

Salam

et al. 2007

Journal of Cell Science

245

215

View full text Add to dashboard Cite

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“…The phosphorylation of HMGB1 in vertebrate cells has not been reported. Another modification profile of HMGB1 is the acetylation of Lys 2 and Lys 11 (28,29), and of only Lys 2 (30) in the N-terminal region of the protein from Guerin ascites tumor cells by sodium butyrate treatment. The binding affinity of acetylated HMGB1 for UVdamaged, cis-platinated, and four-way junction DNA is significantly higher than that of the unmodified protein.…”

Section: Discussionmentioning

confidence: 99%

Post-translational Methylation of High Mobility Group Box 1 (HMGB1) Causes Its Cytoplasmic Localization in Neutrophils

Ito

Fukazawa

Yoshida

2007

Journal of Biological Chemistry

201

187

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High mobility group box 1 (HMGB1) protein plays multiple roles in transcription, replication, and cellular differentiation. HMGB1 is also secreted by activated monocytes and macrophages and passively released by necrotic or damaged cells, stimulating inflammation. HMGB1 is a novel antigen of antineutrophil cytoplasmic antibodies (ANCA) observed in the sera of patients with ulcerative colitis and autoimmune hepatitis, suggesting that HMGB1 is secreted from neutrophils to the extracellular milieu. However, the actual distribution of HMGB1 in the cytoplasm of neutrophils and the mechanisms responsible for it are obscure. Here we show that HMGB1 in neutrophils is post-translationally mono-methylated at Lys 42 . The methylation alters the conformation of HMGB1 and weakens its DNA binding activity, causing it to become largely distributed in the cytoplasm by passive diffusion out of the nucleus. Thus, post-translational methylation of HMGB1 causes its cytoplasmic localization in neutrophils. This novel pathway explains the distribution of nuclear HMGB1 to the cytoplasm and is important for understanding how neutrophils release HMGB1 to the extracellular milieu. High mobility group box 1 (HMGB1)2 protein is one of the most abundant nonhistone chromosomal proteins in eukaryotic organisms. The primary sequences of HMGB1 in various higher organisms, from birds to mammals, show more than 90% homology with each other (1). The protein has multiple roles in transcription, replication, and cellular differentiation (2, 3). HMGB1 interacts with several transcription factors, thereby allowing them to perform their cellular roles. The phenotype of Hmgb1 knock-out mice confirmed the functional importance of HMGB1 as a regulator of transcription: they die shortly after birth and show a defect in the transcriptional control exerted by the glucocorticoid receptor (4). The subcellular distribution of the protein is tissue-specific: HMGB1 is located in both the nuclei and the cytoplasm of different tissues, such as lymphoid tissue, testis, neurons, and hepatocytes (5). Wang et al. (6) identified HMGB1 as a late mediator of endotoxin lethality in mice and showed that monocytes and macrophages stimulated by lipopolysaccharide (LPS), tumor necrosis factor (TNF) or interleukin-1 (IL-1) secrete HMGB1 in a delayed response. Patients with sepsis show an increased serum level of HMGB1, which is correlated with the severity of infection (7). Moreover, HMGB1 in monocytes and macrophages is extensively acetylated upon activation by LPS, causing localization of the protein to the cytosol (8). Cytosolic HMGB1 is then concentrated into secretory lysosomes and secreted when the cells receive an appropriate second signal (9). The recent discovery of extracellular HMGB1 as a proinflammatory mediator has been supported by a number of studies. In addition, HMGB1 is passively released from the nucleus to the extracellular milieu by cells that die as a result of necrosis or damage (10).Our previous studies showed that HMGB1 and HMGB2 are novel antigens of a...

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“…Moreover, both HMGB1 and HMGB2 were acetylated/deacetylated by the same enzymes as those acting on histone H4, indicating the roles of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in the dynamic acetylation of HMGB proteins [109]. Further studies revealed that the acetylated HMGB1 protein, isolated from cells grown in the presence of sodium n-butyrate, exhibited significantly enhanced ability to recognize UV light-or cisplatin-damaged DNA and four-way junction, and the modification site was Lys-2 [110]. In addition, it was found that HMGB1 and HMGB2 were in-vitro substrates for CBP, but not for PCAF or Tip60, and the full-length HMGB1 and HMGB2 were monoacetylated at Lys-2 [111].…”

Section: Ptms Of Hmgb Proteinsmentioning

confidence: 99%

High mobility group proteins and their post-translational modifications

Zhang

Wang

2008

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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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.

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In Vivo Acetylation of HMG1 Protein Enhances Its Binding Affinity to Distorted DNA Structures

Cited by 59 publications

References 54 publications

HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions

HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions

Post-translational Methylation of High Mobility Group Box 1 (HMGB1) Causes Its Cytoplasmic Localization in Neutrophils

High mobility group proteins and their post-translational modifications

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