Carbon dots (CDs) possess unique optical properties such as tunable photoluminescence (PL) and excitation dependent multicolor emission. The quenching and recovery of the fluorescence of CDs can be utilized for detecting analytes. The PL mechanisms of CDs have been discussed in previous articles, but the quenching mechanisms of CDs have not been summarized so far. Quenching mechanisms include static quenching, dynamic quenching, Förster resonance energy transfer (FRET), photoinduced electron transfer (PET), surface energy transfer (SET), Dexter energy transfer (DET) and inner filter effect (IFE). Following an introduction, the review (with 88 refs.) first summarizes the various kinds of quenching mechanisms of CDs (including static quenching, dynamic quenching, FRET, PET and IFE), the principles of these quenching mechanisms, and the methods of distinguishing these quenching mechanisms. This is followed by an overview on applications of the various quenching mechanisms in detection and imaging.

Tumorigenesis is caused by an uncontrolled cell cycle and the altered expression of many genes. Here, we report a gene CREPT that is preferentially expressed in diverse human tumors. Overexpression of CREPT accelerates tumor growth, whereas depletion of CREPT demonstrates a reversed effect. CREPT regulates cyclin D1 expression by binding to its promoter, enhancing its transcription both in vivo and in vitro, and interacting with RNA polymerase II (RNAPII). Interestingly, CREPT promotes the formation of a chromatin loop and prevents RNAPII from reading through the 3' end termination site of the gene. Our findings reveal a mechanism where CREPT increases cyclin D1 transcription during tumorigenesis, through enhancing the recruitment of RNAPII to the promoter region, possibly, as well as chromatin looping.

The severe acute respiratory syndrome (SARS) has been one of the most epidemic diseases threatening human health all over the world. Based on clinical studies, SARSCoV (the SARS-associated coronavirus), a novel coronavirus, is reported as the pathogen responsible for the disease. To date, no e¡ective and speci¢c therapeutic method can be used to treat patients su¡ering from SARS-CoV infection. RNA interference (RNAi) is a process by which the introduced small interfering RNA (siRNA) could cause the degradation of mRNA with identical sequence speci¢city. The RNAi methodology has been used as a tool to silence genes in cultured cells and in animals. Recently, this technique was employed in anti-virus infections in human immunode¢ciency virus and hepatitis C/B virus. In this study, RNAi technology has been applied to explore the possibility for prevention of SARS-CoV infection. We constructed speci¢c siRNAs targeting the S gene in SARS-CoV. We demonstrated that the siRNAs could e¡ectively and speci¢cally inhibit gene expression of Spike protein in SARS-CoV-infected cells. Our study provided evidence that RNAi could be a tool for inhibition of SARS-CoV. ß 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

Currently, a new technology termed PROTAC, proteolysis targeting chimera, has been developed for inducing the protein degradation by a targeting molecule. This technology takes advantage of a moiety of targeted protein and a moiety of recognizing E3 ubiquitin ligase and produces a hybrid molecule to specifically knock down a targeted protein. During the first decade, three pedigreed groups worked on the development of this technology. To date, this technology has been extended by different groups, aiming to develop new drugs against different diseases including cancers. This review summarizes the contributions of the groups for the development of PROTAC. Significance of the study This review summarized the development of the PROTAC technology for readers and also presented the author's opinions on the application of the technology in tumor therapy.

Runx2, an essential transactivator for osteoblast differentiation, is tightly regulated at both the transcriptional and posttranslational levels. In this paper, we report that CHIP (C terminus of Hsc70-interacting protein)/STUB1 regulates Runx2 protein stability via a ubiquitination-degradation mechanism. CHIP interacts with Runx2 in vitro and in vivo. In the presence of increased Runx2 protein levels, CHIP expression decreases, whereas the expression of other E3 ligases involved in Runx2 degradation, such as Smurf1 or WWP1, remains constant or increases during osteoblast differentiation. Depletion of CHIP results in the stabilization of Runx2, enhances Runx2-mediated transcriptional activation, and promotes osteoblast differentiation in primary calvarial cells. In contrast, CHIP overexpression in preosteoblasts causes Runx2 degradation, inhibits osteoblast differentiation, and instead enhances adipogenesis. Our data suggest that negative regulation of the Runx2 protein by CHIP is critical in the commitment of precursor cells to differentiate into the osteoblast lineage.

Drug combination therapy has the potential to enhance efficacy, reduce dose-dependent toxicity and prevent the emergence of drug resistance. However, discovery of synergistic and effective drug combinations has been a laborious and often serendipitous process. In recent years, identification of combination therapies has been accelerated due to the advances in high-throughput drug screening, but informatics approaches for systems-level data management and analysis are needed. To contribute toward this goal, we created an open-access data portal called DrugComb (https://drugcomb.fimm.fi) where the results of drug combination screening studies are accumulated, standardized and harmonized. Through the data portal, we provided a web server to analyze and visualize users’ own drug combination screening data. The users can also effectively participate a crowdsourcing data curation effect by depositing their data at DrugComb. To initiate the data repository, we collected 437 932 drug combinations tested on a variety of cancer cell lines. We showed that linear regression approaches, when considering chemical fingerprints as predictors, have the potential to achieve high accuracy of predicting the sensitivity of drug combinations. All the data and informatics tools are freely available in DrugComb to enable a more efficient utilization of data resources for future drug combination discovery.

Impaired phosphatase activity contributes to the persistent activation of STAT3 in tumors. Given that STAT family members with various or even opposite functions are often phosphorylated or dephosphorylated by the same enzymes, the mechanism for STAT3-specific dephosphorylation in cells remains largely unknown. Here, we report that GdX (UBL4A) promotes STAT3 dephosphorylation via mediating the interaction between TC45 (the nuclear isoform of TC-PTP) and STAT3 specifically. GdX stabilizes the TC45-STAT3 complex to bestow upon STAT3 an efficient dephosphorylation by TC45. Inasmuch, GdX suppresses tumorigenesis and tumor development by reducing the level of phospho-STAT3 (p-STAT3), whereas deletion of GdX results in a high level of p-STAT3 and accelerated colorectal tumorigenesis induced by AOM/DSS. Thus, GdX converts TC45, a nonspecific phosphatase, into a STAT3-specific phosphatase by bridging an association between TC45 and STAT3.

IntroductionSignal transducer and activator of transcription 3 (STAT3) is over-activated or phosphorylated in breast cancers. The hyper-phosphorylation of STAT3 was attributed to either up-regulated phosphorylation by several tyrosine-kinases or down-regulated activity of phosphatases. Although several factors have been identified to phosphorylate STAT3, it remains unclear how STAT3 is dephosphorylated by PTPMeg2. The aim of this study was to determine the role of PTPMeg2 as a phosphatase in regulation of the activity of STAT3 in breast cancers.MethodsImmunoprecipitation assays were used to study the interaction of STAT3 with PTPMeg2. A series of biochemistry experiments were performed to evaluate the role of PTPMeg2 in the dephosphorylation of STAT3. Two breast cancer cell lines MCF7 (PTPMeg2 was depleted as it was endogenously high) and MDA-MB-231 (PTPMeg2 was overexpressed as it was endogenously low) were used to compare the level of phosphorylated STAT3 and the tumor growth ability in vitro and in vivo. Samples from breast carcinoma (n = 73) were subjected to a pair-wise Pearson correlation analysis for the correlation of levels of PTPMeg2 and phosphorylated STAT3.ResultsPTPMeg2 directly interacts with STAT3 and mediates its dephosphorylation in the cytoplasm. Over-expression of PTPMeg2 decreased tyrosine phosphorylation of STAT3 while depletion of PTPMeg2 increased its phosphorylation. The decreased tyrosine phosphorylation of STAT3 is coupled with suppression of STAT3 transcriptional activity and reduced tumor growth in vitro and in vivo. Levels of PTPMeg2 and phosphorylated STAT3 were inversely correlated in breast cancer tissues (P = 0.004).ConclusionsPTPMeg2 is an important phosphatase for the dephosphorylation of STAT3 and plays a critical role in breast cancer development.