Antigenic determinants of high mobility group chromosomal proteins 1 and 2

Bustin, Michael; Dunn, Barbara K.; Gillette, R; Mendelsohn, Ella; Soares, Nirmolini

doi:10.1021/bi00269a024

Cited by 9 publications

(6 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, a perinuclear staining pattern of HMG1/HMG2 autoantibodies that develop in patients with refractory ulcerative colitis has been previously reported (50). Autoantibodies to HMG1 and HMG2 have also been found in patients with systemic lupus erythematosis and juvenile rheumatoid arthritis (15,63). One theory is that autoantibodies arise to proteins and other compounds modified during apoptosis.…”

Section: Discussionmentioning

confidence: 89%

HMG2 Interacts with the Nucleosome Assembly Protein SET and Is a Target of the Cytotoxic T-Lymphocyte Protease Granzyme A

Fan

Beresford

Zhang

et al. 2002

Molecular and Cellular Biology

126

View full text Add to dashboard Cite

The cytotoxic T-lymphocyte protease granzyme A induces caspase-independent cell death in which DNA single-stranded nicking is observed instead of oligonucleosomal fragmentation. A 270-to 420-kDa endoplasmic reticulum-associated complex (SET complex) containing the nucleosome assembly protein SET, the tumor suppressor pp32, and the base excision repair enzyme APE can induce single-stranded DNA damage in isolated nuclei in a granzyme A-dependent manner. The normal functions of the SET complex are unknown, but the functions of its components suggest that it is involved in activating transcription and DNA repair. We now find that the SET complex contains DNA binding and bending activities mediated by the chromatin-associated protein HMG2. HMG2 facilitates assembly of nucleoprotein higher-order structures by bending and looping DNA or by stabilizing underwound DNA. HMG2 is in the SET complex and coprecipitates with SET. By confocal microscopy, it is observed that cytoplasmic HMG2 colocalizes with SET in association with the endoplasmic reticulum, but most nuclear HMG2 is unassociated with SET. This physical association suggests that HMG2 may facilitate the nucleosome assembly, transcriptional activation, and DNA repair functions of SET and/or APE. HMG2, like SET and APE, is a physiologically relevant granzyme A substrate in targeted cells. HMG1, however, is not a substrate. Granzyme A cleavage after Lys65 in the midst of HMG box A destroys HMG2-mediated DNA binding and bending functions. Granzyme A cleavage and functional disruption of key nuclear substrates, including HMG2, SET, APE, lamins, and histones, are likely to cripple the cellular repair response to promote cell death in this novel caspase-independent death pathway.

show abstract

Section: Discussionmentioning

confidence: 89%

HMG2 Interacts with the Nucleosome Assembly Protein SET and Is a Target of the Cytotoxic T-Lymphocyte Protease Granzyme A

Fan

Beresford

Zhang

et al. 2002

Molecular and Cellular Biology

126

View full text Add to dashboard Cite

show abstract

“…In the present study we show that oocytes of various amphibian species contain large amounts of a soluble form of one HMG protein, HMG-A, which is accumulated in the nucleus but is also found in the cytoplasm. We further show that antibodies against mammalian HMG-1 and -2 (32)(33)(34), when microinjected into these nuclei, interfere with transcriptional events in the lampbrush chromosomes.…”

mentioning

confidence: 70%

“…antibodies to HMG proteins from calf thymus have been described (19,(32)(33)(34). Immunofluorescence microscopy using cryostat sections through frozen ovaries of adult females of the species studied was essentially as described (28).…”

Section: Antibodies and Immunofluorescence Microscopy: Rabbitmentioning

confidence: 99%

High mobility group proteins of amphibian oocytes: a large storage pool of a soluble high mobility group-1-like protein and involvement in transcriptional events.

Kleinschmidt¹,

Scheer²,

Dabauvalle³

et al. 1983

The Journal of Cell Biology

View full text Add to dashboard Cite

Oocytes of several amphibian species (Xenopus laevis, Rana temporaria, andPleurodeles waltlii) contained a relatively large pool of nonchromatin-bound, soluble high mobility group (HMG) protein with properties similar to those of calf thymus proteins HMG-1 and HMG-2 (protein HMG-A; A, amphibian). About half of this soluble HMG-A was located in the nuclear sap, the other half was recovered in enucleated ooplasms. This protein was identified by its mobility on one-and two-dimensional gel electrophoresis, by binding of antibodies to calf thymus HMG-1 to polypeptides electrophoretically separated and blotted on nitrocellulose paper, and by tryptic peptide mapping of radioiodinated polypeptides. Most, if not all, of the HMG-A in the soluble nuclear protein fraction, preparatively defined as supernatant obtained after centrifugation at 100,000 g for 1 h, was in free monomeric form, apparently not bound to other proteins. On gel filtration it eluted with a mean peak corresponding to an apparent molecular weight of ,-25,000; on sucrose gradient centrifugation it appeared with a very low S value (2-3 S), and on isoelectric focusing it appeared in fractions ranging from pH ~7 to 9. This soluble HMG-A was retained on DEAE-Sephacel but could be eluted already at moderate salt concentrations (0.2 M KCI). In oocytes of various stages of oogenesis HMG-A was accumulated in the nucleus up to concentrations of ~14 ng per nucleus (in Xenopus), corresponding to --0.2 mg/ml, similar to those of the nucleosomal core histones. This nuclear concentration is also demonstrated using immunofluorescence microscopy. When antibodies to bovine HMG-1 were microinjected into nuclei of living oocytes of Pleurodeles the lateral loops of the lampbrush chromosomes gradually retracted and the whole chromosomes condensed. As shown using electron microscopy of spread chromatin from such injected oocyte nuclei, this process of loop retraction was accompanied by the appearance of variously-sized and irregularly-spaced gaps within transcriptional units of chromosomal loops but not of nucleoli, indicating that the transcription of non-nucleolar genes was specifically inhibited by this treatment and hence involved an HMG-l-like protein.These data show that proteins of the HMG-1 and -2 category, which are usually chromatinbound components, can exist, at least in amphibian oocytes, in a free soluble monomeric form, apparently not bound to other molecules. The possible role of this large oocyte pool of soluble HMG-A in early embryogenesis is discussed as well as the possible existence of soluble HMG proteins in other cells.The high mobility group (HMG) I proteins are a family of Abbreviations used in thispaper: HMG, high mobility group; PCA, perchloric acid; TCA, trichloroacetic acid. 838 nonhistone components of chromatin that are of relatively low molecular weight (Mr 7,000), contain high proportions of both positively and negatively charged residues distributed in a polar fashion, can be extracted from chro-

show abstract

“…Dating to the seminal studies of Bustin et al in 1982 [122], HMG antibodies have been reported in SLE [122–124], mixed connective tissue disease [122], juvenile idiopathic arthritis (JIA) [125–128], canine lupus [129], DIL [130], systemic sclerosis [131], other systemic autoimmune rheumatic diseases [132], primary pulmonary hypertension [133], inflammatory bowel disease [134–136], primary biliary cirrhosis [137], type I diabetes [138], autoimmune hepatitis [139], septic shock [140], and liver transplant patients (see Table 2 for more details) [141, 142]. …”

Section: Future Areas Of Interestmentioning

confidence: 99%

The Spectrum of Anti-Chromatin/Nucleosome Autoantibodies: Independent and Interdependent Biomarkers of Disease

Mehra

Fritzler

2014

Journal of Immunology Research

View full text Add to dashboard Cite

Autoantibodies directed to chromatin components date back to the discovery of the LE cell and the LE cell phenomenon circa 1950, and subsequent evidence that major components of that reaction were chromatin components and histones in particular. Over time, immunoassays ranging from ELISA and line immunoassays to more modern bead-based assays incorporated histone and DNA mixtures, purified histones, and purified nucleosomes leading to a more thorough understanding of the genesis and pathogenetic relationships of antibodies to chromatin components in systemic lupus erythematosus and other autoimmune conditions. More recently, interest has focussed on other components of chromatin such as high mobility group (HMG) proteins both as targets of B cell responses and pro-inflammatory mediators. This review will focus on immunoassays that utilize chromatin components, their clinical relationships, and newer evidence implicating HMG proteins and DNA neutrophil extracellular traps (NETs) as important players in systemic autoimmune rheumatic diseases.

show abstract

Antigenic determinants of high mobility group chromosomal proteins 1 and 2

Cited by 9 publications

References 17 publications

HMG2 Interacts with the Nucleosome Assembly Protein SET and Is a Target of the Cytotoxic T-Lymphocyte Protease Granzyme A

HMG2 Interacts with the Nucleosome Assembly Protein SET and Is a Target of the Cytotoxic T-Lymphocyte Protease Granzyme A

High mobility group proteins of amphibian oocytes: a large storage pool of a soluble high mobility group-1-like protein and involvement in transcriptional events.

The Spectrum of Anti-Chromatin/Nucleosome Autoantibodies: Independent and Interdependent Biomarkers of Disease

Contact Info

Product

Resources

About