Transformation growth factor β -inducible gene 22 (TSC-22) is a putative negative growth regulation and tumor suppressor gene. It has the ability to combine with other transcription factors to regulate the cell growth and apoptosis. TSC-22 is lowly expressed in many types of tumors,which may be related to the tumorgenesis and development.
Animals ; Genes, Tumor Suppressor ; Humans ; Leucine Zippers ; genetics ; Neoplasms ; physiopathology ; Repressor Proteins ; genetics ; physiology ; Transcription Factors

Dysregulation of the Wnt pathway has been extensively studied in multiple diseases, including some angiogenic disorders. Wnt signaling activation is a major stimulator in pathological angiogenesis and thus, Wnt antagonists are believed to have therapeutic potential for neovascular disorders. Actually, some Wnt antagonists have been identified directly from the anti-angiogenic factor family. This review summarizes the recent progress toward understanding of the roles of Wnt pathway antagonists in angiogenic regulation and their mechanism of action, and exploring their therapeutic potential.
Adaptor Proteins, Signal Transducing ; metabolism ; Animals ; Humans ; Neovascularization, Pathologic ; physiopathology ; Repressor Proteins ; metabolism ; Signal Transduction ; physiology ; Wnt Proteins ; antagonists & inhibitors

Common warts are close associated with HPVs infection. In this study, we amplified and sequenced the LCR fragment and E2 gene of HPV-2 that infected the patient of extensive common wart with cutaneous horns, and we constructed the recombinant CAT-reporter plasmids pBLCAT-LCR containing HPV-2 prototype or variant LCR and mammalian expression plasmids pcDNA3. 1-E2 containing prototype or variant E2 ORF individually. The promoter activities of HPV-2 variant and the transcriptional repression activities of the mutated E2 protein were evaluated by transient transfection into HeLa cells. The results showed that there were several mutations in LCR and E2 gene of HPV-2 variant. Compared with the prototype, the viral early promoter activity of variant was significantly increased uder the control of LCR. Compared with the wild type E2 protein, the transcriptional repression activities of the mutated E2 protein was abolished partially. We speculate herein that increased promoter activities and decreased repression effect of the mutated E2 protein are linked, at least partially, with the clinical phenotypes of the uncommon huge common wart.
DNA-Binding Proteins ; genetics ; physiology ; Humans ; Mutation ; Oncogene Proteins, Viral ; genetics ; physiology ; Papillomaviridae ; genetics ; Promoter Regions, Genetic ; Repressor Proteins ; physiology ; Warts ; virology

By means of a circadian clock system, all the living organisms on earth including human beings can anticipate the environmental rhythmic changes such as light/dark and warm/cold periods in a daily as well as in a yearly manner. Anticipating such environmental changes provide organisms with survival benefits via manifesting behavior and physiology at an advantageous time of the day and year. Cell-autonomous circadian oscillators, governed by transcriptional feedback loop composed of positive and negative elements, are organized into a hierarchical system throughout the organisms and generate an oscillatory expression of a clock gene by itself as well as clock controlled genes (ccgs) with a 24 hr periodicity. In the feedback loop, hetero-dimeric transcription factor complex induces the expression of negative regulatory proteins, which in turn represses the activity of transcription factors to inhibit their own transcription. Thus, for robust oscillatory rhythms of the expression of clock genes as well as ccgs, the precise control of subcellular localization and/or timely translocation of core clock protein are crucial. Here, we discuss how sub-cellular localization and nuclear translocation are controlled in a time-specific manner focusing on the negative regulatory clock proteins.
Circadian Clocks* ; Circadian Rhythm ; CLOCK Proteins ; Humans ; Periodicity ; Phosphorylation ; Physiology ; Protein Processing, Post-Translational ; Repressor Proteins* ; Transcription Factors

Self-renewal of hematopoietic stem cells is vital for the sustained daily production of blood cells. The Bmi-1 gene is a putative oncogene belonging to the Polycomb group family. Recent studies have shown that the Polycomb-group gene Bmi-1 is indispensable for regulation of self-renewal of normal and leukemic stem cells. The research progress on structure and function of Bmi-1 gene, and its role in self-renewal of hematopoietic stem cells was reviewed.
Cell Differentiation ; physiology ; Cell Division ; physiology ; Hematopoietic Stem Cells ; cytology ; physiology ; Humans ; Nuclear Proteins ; genetics ; physiology ; Polycomb Repressive Complex 1 ; Proto-Oncogene Proteins ; genetics ; physiology ; Repressor Proteins ; genetics ; physiology

PURPOSE: The role of the Ferric Uptake Regulator (FUR) in the acid resistance of Helicobacter pylori (H. pylori) has been thought to be independent of urease. However, we demonstrated in this study that Fur influences urease activity. MATERIALS AND METHODS: A fur knockout mutant of H. pylori was constructed by replacing the Fur gene with a kanamycin resistant marker gene. The wild-type H. pylori and fur mutant were compared for survival. The integrity of the inner membrane of the bacteria was evaluated by confocal microscopy using membrane-permeant and -impermeant fluorescent DNA probes. Urease activity of intact H. pylori was measured between pH 3 and 8. Real time PCR of both strains was performed for urease genes including ureI, ureE, ureF, ureG, and ureH. RESULTS: The fur deletion affected the survival of H. pylori at pH 4. The urease activity curve of the intact fur mutant showed the same shape as the wild-type but was 3-fold lower than the wild-type at a pH of less than 5. Real time PCR revealed that the expression of all genes was consistently down-regulated in the fur mutant. CONCLUSION: The results of this study showed that fur appears to be involved in acid resistant H. pylori urease activity.
Bacterial Proteins/genetics/*physiology ; Helicobacter pylori/*enzymology/genetics ; Hydrogen-Ion Concentration ; Microscopy, Confocal ; Models, Biological ; Mutation ; Repressor Proteins/genetics/*physiology ; Urease/*metabolism

Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer and is the second leading cause of cancer mortality with an estimated 745 500 deaths annually (Jemal et al., 2011). Although new therapeutic modalities including novel chemotherapeutic interventions and targeted therapy have been applied, the prognosis of HCC patients remains unsatisfactory due to the high incidence of intrahepatic and distal metastases (Siegel et al., 2018).
Apoptosis Regulatory Proteins/physiology* ; Biomarkers ; Carcinoma, Hepatocellular/pathology* ; Female ; Genome ; Humans ; Hypoxia ; Liver Neoplasms/pathology* ; Male ; MicroRNAs/analysis* ; Neoplasm Staging ; Prognosis ; Repressor Proteins/physiology*

OBJECTIVETo screen the asymmetric dimethyl arginines (ADMA)-containing proteins which could combine with protein arginine methyltransferase 1 (PRMT1).

METHODSWestern blot was adopted to identify the expression of PRMT1 and the proteins with ADMA in glioma cell lines and normal brain tissues, and then to detect the changes of ADMA level after knock-down of PRMT1 with RNAi transfection in U87MG cells. Co-Immunoprecipitation (Co-IP), western blot, and sliver staining were employed to screen the candidate binding proteins of PRMT1. Then liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify the binding proteins of PRMT1.

RESULTSThe expression of PRMT1 and some levels of ADMA were higher in glioma cell lines than in normal brain tissues. After knocking down PRMT1, some ADMA levels were found declined. After screening the binding proteins of PRMT1 with Co-IP and LC-MS/MS, 26 candidate binding proteins were identified. Among them, 6 candidate proteins had higher ions scores (> 38) and bioinformation analysis predicted that SEC23-IP, ANKHD1-EIF4EBP3 protein, and 1-phosphatidylinositol-3-phosphate 5-kinase isoform 2 had possible methylated aginine sites.

CONCLUSIONSThe high expression of PRMT1 in glioma may induce the change of ADMA levels. Altogether 26 candidate proteins were identified, which contain ADMA and specifically bind with PRMT1.

Arginine ; analogs & derivatives ; analysis ; Cell Line, Tumor ; Chromatography, Liquid ; Glioma ; chemistry ; Humans ; Immunoprecipitation ; Protein-Arginine N-Methyltransferases ; analysis ; physiology ; Repressor Proteins ; analysis ; physiology ; Substrate Specificity ; Tandem Mass Spectrometry

While it is known that spermatogonial stem cells (SSCs) initiate the production of male germ cells, the mechanisms of SSC self-renewal, proliferation, and differentiation remain poorly understood. We have previously identified Strawberry Notch 1 (SBNO1), a vertebrate strawberry notch family protein, in the proteome profile for mouse SSC maturation and differentiation, revealing SBNO1 is associated with neonatal testicular development. To explore further the location and function of SBNO1 in the testes, we performed Sbno1 gene knockdown in mice to study the effects of SBNO1 on neonatal testicular and SSC development. Our results revealed that SBNO1 is required for neonatal testicular and SSC development in mice. Particularly, in vitro Sbno1 gene knockdown with morpholino oligonucleotides caused a reduction of SSCs and inactivation of the noncanonical Wnt pathway, through Jun N-terminal kinases. Our study suggests SBNO1 maintains SSCs by promoting the noncanonical Wnt pathway.
Adult Germline Stem Cells/metabolism* ; Animals ; Cell Proliferation/physiology* ; Gene Knockdown Techniques ; Male ; Mice ; Proteome ; Repressor Proteins/metabolism* ; Testis/metabolism* ; Wnt Signaling Pathway/physiology*

OBJECTIVETo study the regulatory rolesof SIRT1 on EZH2 expression and the further effects on EZH 2’ s repression of target gene expression.

METHODSThe stable SIRT1 RNAi and Control RNAi HeLa cells were established by infection with retroviruses expressing shSIRT1 and shLuc respectively followed by puromycin selection. EZH2 protein level was detected by Western blot in either whole cell lysate or the fractional cell extract. Reverse transcription-polymerase chain reaction was performed to detect the mRNA level of EZH2. Cycloheximide was used to treat SIRT1 RNAi and Control RNAi cells for protein stability assay. Chromatin immunoprecipitation(ChIP) assay was applied to measure enrichment of SIRT1, EZH2, and trimethylated H3K27 (H3K27me3) at SATB1 promoter in SIRT1 RNAi and Control RNAi cells.

RESULTSWestern blot results showed that EZH2 protein level increased upon SIRT1 depletion. Fractional extraction results showed unchanged cytoplasmic fraction and increased chromatin fraction of EZH2 protein in SIRT1 RNAi cells. The mRNA level of EZH2 was not affected by knockdown of SIRT1. SIRT1 recruitment was not detected at the promoter regionof EZH2 gene locus. The protein stability assay showed that the protein stability of EZH2 increases upon SIRT1 knockdown. Upon SIRT1 depletion, EZH2 and H3K27me3 recruitment at SATB1 promoter increases and the mRNA level of SATB1 decreases.

CONCLUSIONSDepletion of SIRT1 increases the protein stability of EZH2. The regulation of EZH2 protein level by SIRT1 affects the repressive effects of EZH2 on the target gene expression.

DNA-Binding Proteins ; analysis ; chemistry ; physiology ; Enhancer of Zeste Homolog 2 Protein ; Gene Expression Regulation ; HeLa Cells ; Humans ; Polycomb Repressive Complex 2 ; Repressor Proteins ; physiology ; Sirtuin 1 ; antagonists & inhibitors ; physiology ; Transcription Factors ; analysis ; chemistry ; physiology