Protein phosphatase-1 (PP1) nuclear targeting subunit (PNUTS), also called PP1R10, p99, or CAT 53 was originally isolated as a mammalian nuclear PP1-binding protein. In this study, we performed yeast two-hybrid screens to identify PNUTS-interacting proteins. Here, we report that LCP1 (epidermal Langerhans cell protein 1), a novel member of the HMG-box protein family, binds tightly to PNUTS. Co-immunoprecipitation of deletion constructs revealed that the C-terminus of LCP1 is sufficient for the interaction with an N-terminal region of PNUTS that is distinct from its PP1-binding domain. Furthermore, immunofluorescence studies showed that a subpopulation of LCP1 co-localizes with PNUTS in nuclear speckles. Importantly, we found that the N-terminus of LCP1 has a strong trans-activation activity in a GAL4-based heterologous transcription assay. The transcriptional activity of LCP1 is markedly suppressed by its interaction with PNUTS, in a PP1-independent manner. These findings suggest that the coordinated spatial and temporal regulation of LCP1 and PNUTS may be a novel mechanism to control the expression of genes that are critical for certain physiological and pathological processes.
Amino Acid Sequence ; Cell Line ; Cell Nucleus/*metabolism ; DNA-Binding Proteins/*metabolism ; HMGB Proteins/*metabolism ; Humans ; Molecular Sequence Data ; Nuclear Proteins/*metabolism ; Protein Binding ; Protein Interaction Mapping ; RNA-Binding Proteins/*metabolism ; Transcriptional Activation ; Two-Hybrid System Techniques

OBJECTIVETo investigate the association between high mobility group box1 (HMGB1) and cervical squamous cell carcinoma (CSCC), and explore the role of HMGB1/RAGE pathway in the metastasis of CSCC.

METHODSLevels of HMGB1 mRNA and RAGE mRNA in CSCC and normal cervical tissues were detected by real time quantitative polymerase chain reaction (qRT-PCR), and the level of HMGB1 protein was determined by immunohistochemistry and Western blotting.

RESULTSThe mRNA and protein expression of HMGB1 was significantly higher in CSCC than that in normal cervical tissue (P < 0.05), correlated with stage, invasion and metastasis (P < 0.05), but not with tumor size and differentiation (P > 0.05). The levels of RAGE mRNA and HMGB1 mRNA were both significantly higher (r = 0.663, P < 0.05) in metastatic CSCC in comparison with those in the non-metastatic cases.

CONCLUSIONHMGB1 is involved in the invasion and metastasis of CSCC, and HMGB1/RAGE pathway plays an important role in the metastasis of CSCC.

Blotting, Western ; Carcinoma in Situ ; metabolism ; pathology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cervix Uteri ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; HMGB Proteins ; metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; RNA, Messenger ; metabolism ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Uterine Cervical Neoplasms ; metabolism ; pathology

No abstract available.
HMGB1 Protein* ; Pemphigus*

Humans ; Asthma/diagnosis* ; HMGB1 Protein

HMGB1 is a widely existing DNA-binding nuclear protein, participating in gene transcription, damage repair, recombination and stabilizing nucleosome construction. Under injury, infection and chemotherapy, HMGB1 can be released by nature immunocyte and necrosis cells as a DAMP, exerting pleiotropic biological effects by binding to RAGE, TLR and CXCL12, which lead to activation of CDC42, mitogen-activated protein kinases (MAPKs), c-IAP and NF-κB, thereby promoting angiogenesis, unlimited replicative potential, tissue invasion and metastasis. And it also involves in immune response by regulating immunocyte function as a immunocyte warning signal. Scholars have detected that HMGB1 is over expressed and released following chemotherapy and radiation therapy in cells of hematological malignancies, promoting malignant cell replication, decreasing therapeutic effect. Recently, endogenous HMGB1 has been implied to be an intrinsic modulator of autophagy and referenced to resistant to apoptosis in malignant hematosis cells. In contrast, through suppression of HMGB1 expression, tumor cell apoptosis and chemotherapeutic drug sensitivity were increased, which will be a new strategy for the treatment of hematological malignancies. In this article, the basic characteristics of HMGB1, including structure and biological features, and HMGB1 and tumors such as lymphoma, myeloproliferative neoplasms and acute myeloid leukemia are reviewed.
Animals ; HMGB1 Protein ; Hematologic Neoplasms ; therapy ; Humans

Endotoxemia ; metabolism ; pathology ; HMGB1 Protein ; Humans ; Liver ; metabolism ; pathology

High mobility group box-1 protein (HMGB1), which is a nuclear protein, participates in chromatin architecture and transcriptional regulation. When released from cells, HMGB1 also plays a well-established role as a pro-inflammatory mediator during innate immune responses to injury. In the initial stage of injury, there is a release of large quantities of early pro-inflammatory mediators to initiate or perpetuate immune responses against pathogens, but this pro-inflammatory period is transient, and it is followed by a prolonged period of immune suppression. At present, several lines of evidences have suggested that HMGB1 is a late cytokine provoking delayed endotoxin morbidity, which may enhance the production of early proinflammatory mediators, and it can contribute potently to the activation of different immune cells and play a role in the development of host cell-mediated immunity. The biology of HMGB1 has been extensively studied as a pro-inflammatory cytokine of systemic inflammation, however, this review will attempt to provide a summary of the effects of HMGB1 on different immune cells and its regulatory mechanism in acute insults.
Cytokines ; immunology ; HMGB1 Protein ; immunology ; Humans ; Immunity, Cellular ; Inflammation ; immunology

OBJECTIVETo investigate the significance of changes in plasma high mobility group box-1 protein (HMGB1) levels and its relationship with sepsis and endotojemia in severely burned patients.

METHODSTotally 25 large area burned patients ( > 30% total body surface area) were included in this study, and 8 healthy volunteers served as normal controls. The plasma levels of HMGB1 were measured by ELISA, and endotoxin concentrations was determined by the modified chromogenic limulus amebocyte lysate (LAL) assay on posthurn days 1, 3, 5, 7, 14, 21, and 28.

RESULTSThe plasma HMGBL levels were markedly elevated on postburn day 1 in severely burned patients, and they were significantly higher in septic patients than those without sepsis on days 7, 21, and 28 after burns (P<0.05). Among septic patients, plasma HMGBI levels in the survival group were significantly lower than those with fatal outcome on days 3 and 21 (P<0.05, P<0.01). No significant correlations were found between HMGB1 levels and the sizes of total body surface area (P>0.05). In addition, the plasma HMGB1 levels were positively correlated with endotoxin concentrations on days 3, 5, 7, 21 after major burns (P<0.05, P<0.01).

CONCLUSIONSHMGB1, as an important late mediators of inflammation, may be involved in the development of sepsis following extensive burns, and it can be markedly induced by endotoxemia secondary to acute insults. Dynamic measurements of circulating HMGB1 levels should be helpful to monitor the disease course and judge the prognosis of burned patients.

Burns ; blood ; microbiology ; Endotoxins ; blood ; HMGB1 Protein ; blood ; Humans ; Sepsis ; blood

OBJECTIVETo evaluate the value of high mobility group box 1(HMGB1) in the diagnosis of pediatric acute appendicitis.

METHODSThe children with acute abdomen who had a diagnosis of suspected acute appendicitis between January and July 2013 and 25 healthy children were enrolled in this study. Serum HMGB1 levels were measured using ELISA on admission. The patients were classified into 2 groups according to surgery confirmation or pathological results: appendicitis (n=28) and non-appendicitis (n=35).

RESULTSSerum HMGB1 levels and WBC in the appendicitis and non-appendicitis groups were significantly higher than in the healthy children group (P<0.01). The appendicitis group showed more increased serum HMGB1 levels compared with the non-appendicitis group (median: 32.9 ng/mL vs 22.0 ng/mL; P<0.01). For a diagnosis of acute appendicitis, the sensitivity and specificity of serum HMGB1 was 71.4% and 82.9% respectively at the best cutoff of 28.0 ng/mL, with the accuracy of 77.8% and the area under the curve of 0.765 (95%CI 0.638-0.893).

CONCLUSIONSHMGB1 may play a role in the diagnosis of pediatric acute appendicitis.

Acute Disease ; Appendicitis ; blood ; diagnosis ; Child, Preschool ; Female ; HMGB1 Protein ; blood ; Humans ; Infant ; Male

Eosinophils have been reported to modulate T cell responses. Previously, we reported that high-mobility group box 1 protein (HMGB1) played a key role in the pathogenesis of asthma. This study was conducted to test our hypothesis that eosinophils could modulate T cell responses via HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation. We performed in vitro experiments using eosinophils, dendritic cells (DCs), and CD4+ T cells obtained from a murine model of asthma. The supernatant of the eosinophil culture was found to significantly increase the levels of interleukin (IL)-4 and IL-5 in the supernatant of CD4+ T cells co-cultured with DCs. HMGB1 levels increased in the supernatant of the eosinophil culture stimulated with IL-5. Anti-HMGB1 antibodies significantly attenuated increases of IL-4 and IL-5 levels in the supernatant of CD4+ T cells co-cultured with DCs that were induced by the supernatant of the eosinophil culture. In addition, anti-HMGB1 antibodies significantly attenuated the expressions of activation markers (CD44 and CD69) on CD4+ T cells. Our data suggest that eosinophils modulate CD4+ T cell responses via HMGB1 in the pathogenesis of asthma.
Antibodies ; Asthma* ; Dendritic Cells ; Eosinophils* ; HMGB1 Protein ; Inflammation ; Interleukin-4 ; Interleukin-5 ; Interleukins ; T-Lymphocytes