A wireless demodulation system based on a multi-parameter resonant sensor.

This paper proposes a wireless passive measurement system that supports real-time signal acquisition, multi-parameter crosstalk demodulation, and real-time storage and calculation. The system consists of a multi-parameter integrated sensor, an RF signal acquisition and demodulation circuit, and a multi-functional host computer software. The sensor signal acquisition circuit uses a wide frequency detection range (25 MHz-2.7 GHz) to meet the resonant frequency range of most sensors. Since the multi-parameter integrated sensors are affected by multiple factors, such as temperature and pressure, there will be interference between them, so the algorithm for multi-parameter decoupling is designed, and the software for sensor calibration and real-time demodulation is developed to improve the usability and flexibility of the measurement system. In the experiment, temperature and pressure dual-reference integrated surface acoustic wave sensors in the condition of 25-550 °C and 0-700 kPa are used for testing and verification. After experimental testing, the swept source of the signal acquisition circuit can meet the output accuracy in a wide frequency range, and the detection result of the sensor dynamic response is consistent with that of the network analyzer, with a maximum test error of 0.96%. Furthermore, the maximum temperature measurement error is 1.51%, and the maximum pressure measurement error is 5.136%. These results indicate that the proposed system has good detection accuracy and demodulation performance, and it can be used for multi-parameter wireless real-time detection and demodulation.

Effects of Artemisia annua L. Essential Oil on Osteoclast Differentiation and Function Induced by RANKL.

Objective: This study aimed to assess the main components of Artemisia annua L. essential oil (AEO) and determine their effect on the proliferation and differentiation of RAW264.7 cells induced by receptor activator for nuclear factor-ligand (RANKL) in vitro. Then, we tried to explain part of the function of its possible mechanisms. Materials and Methods: Essential oil was extracted from Artemisia annua L. Osteoclasts were induced in vitro by RANKL in mouse RAW264.7 cells. The experimental group was treated with different concentrations of AEO, while the control group was not treated with AEO. CCK8 was used to detect osteoclast proliferation. The osteoclasts were stained with TRAP. Western blot was used to detect protein in the MAPK pathway and the NF-κB pathway after treatment with different concentrations of AEO. RT-PCR was used to determine the expression of osteoclast-related mRNA in cells. Results: The GC-MS analysis was used to obtain the main components of AEO, including camphor, borneol, camphor, borneol, terpinen-4-ol, p-cymene, eucalyptol, deoxyartemisinin, and artemisia ketone. The CCK8 results showed that the AEO volume ratio of 1 : 4000, 1 : 5000, and 1 : 6000 did not affect the proliferation of RAW264.7 cells. However, TRAP staining showed that AEO decreased osteoclast formation. Western blot results showed that the expression of protein TRAF6, p-p38, p-ERK, p-p65, and NFATc1 decreased in the MAPK pathway and the NF-κB pathway affected by AEO. Furthermore, RT-PCR results showed that the expression of osteoclast resorption-related mRNAs (MMP-9, DC-STAMP, TRAP, and CTSK) and osteoclast differentiation-related mRNAs (OSCAR, NFATc1, c-Src, and c-Fos) also decreased in the experimental group. Conclusions: AEO inhibits osteoclast differentiation in vitro, probably by reducing TRAF6 activation, acting on the MAPK pathway and NF-κB pathway, and inhibiting the expression of osteoclast-related genes.

Effective Safety Message Dissemination with Vehicle Trajectory Predictions in V2X Networks.

Exploring data connection information from vehicle-to-vehicle (V2V) and vehicle-to-infrastructure (V2I) communications using advanced machine learning approaches, an intelligent transportation system (ITS) can provide better safety services to mitigate the risk of road accidents and improve traffic efficiency. In this work, we propose an end-edge-cloud architecture to deploy machine learning-driven approaches at network edges to predict vehicles' future trajectories, which is further utilized to provide an effective safety message dissemination scheme. With our approach, the traffic safety message will only be disseminated to relevant vehicles that are predicted to pass by accident areas, which can significantly reduce the network data transmission overhead and avoid unnecessary interference. Depending on the vehicle connectivity, our system adaptively chooses vehicle-to-vehicle (V2V) or vehicle-to-infrastructure (V2I) communications to disseminate safety messages. We evaluate the system by using a real-world VANET mobility dataset, and experimental results show that our system outperforms other mechanisms without considering any predicted vehicle trajectory density information.

Constitutive Expression of the Immunosuppressive Tryptophan Dioxygenase TDO2 in Glioblastoma Is Driven by the Transcription Factor C/EBPß.

Catabolism of the essential amino acid tryptophan is a key metabolic pathway contributing to the immunosuppressive tumor microenvironment and therefore a viable drug target for cancer immunotherapy. In addition to the rate-limiting enzyme indoleamine-2,3-dioxygenase-1 (IDO1), tryptophan catabolism via tryptophan-2,3-dioxygenase (TDO2) is a feature of many tumors, particularly malignant gliomas. The pathways regulating TDO2 in tumors are poorly understood; using unbiased promoter and gene expression analyses, we identify a distinct CCAAT/enhancer-binding protein ß (C/EBPß) binding site in the promoter of TDO2 essential for driving constitutive TDO2 expression in glioblastoma cells. Using The Cancer Genome Atlas (TCGA) data, we find that C/EBPß expression is correlated with TDO2, and both are enriched in malignant glioma of the mesenchymal subtype and associated with poor patient outcome. We determine that TDO2 expression is sustained mainly by the LAP isoform of CEBPB and interleukin-1ß, which activates TDO2 via C/EBPß in a mitogen-activated protein kinase (MAPK) kinase-dependent fashion. In summary, we provide evidence for a novel regulatory and therapeutically targetable pathway of immunosuppressive tryptophan degradation in a subtype of glioblastoma with a particularly poor prognosis.

Tissue Engineering and Regenerative Medicine: Achievements, Future, and Sustainability in Asia.

Exploring innovative solutions to improve the healthcare of the aging and diseased population continues to be a global challenge. Among a number of strategies toward this goal, tissue engineering and regenerative medicine (TERM) has gradually evolved into a promising approach to meet future needs of patients. TERM has recently received increasing attention in Asia, as evidenced by the markedly increased number of researchers, publications, clinical trials, and translational products. This review aims to give a brief overview of TERM development in Asia over the last decade by highlighting some of the important advances in this field and featuring major achievements of representative research groups. The development of novel biomaterials and enabling technologies, identification of new cell sources, and applications of TERM in various tissues are briefly introduced. Finally, the achievement of TERM in Asia, including important publications, representative discoveries, clinical trials, and examples of commercial products will be introduced. Discussion on current limitations and future directions in this hot topic will also be provided.

Polydopamine-assisted surface modification for orthopaedic implants.

Along with the massive use of implants in orthopaedic surgeries in recent few decades, there has been a tremendous demand for the surface modification of the implants to avoid surgery failure and improve their function. Polydopamine (PDA), being able to adhere to almost all kinds of substrates and possessing copious functional groups for covalently immobilizing biomolecules and anchoring metal ions, has been widely used for surface modification of materials since its discovery in the last decade. PDA and its derivatives can be used for the surface modification of orthopaedic implants to modulate cellular responses, including cell spreading, migration, proliferation, and differentiation, and may thereby enhance the function of existing implants. In addition, the osseointegration and antimicrobial properties of orthopaedic implants may also be improved by PDA-based coatings. The aim of this review is to provide a brief overview of current advances of surface modification technologies for orthopaedic implants using PDA and its derivatives as a medium. Given the versatility of PDA-based adhesion, such PDA-assisted surface modification technologies will certainly benefit the development of new orthopaedic implants. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Surface treatments of orthopaedic implants, which are normally inert materials, are essential for their performance in vivo. This review summarizes recent advances in the surface modification of orthopaedic implants using facile and highly versatile techniques based on the use of polydopamine (PDA) and its derivatives.

Preparation of lysozyme-imprinted nanoparticles on polydopamine-modified titanium dioxide using ionic liquid as a stabilizer.

Molecular imprinting of proteins has evolved into an efficient approach for protein recognition and separation. However, maintaining the structural stability of proteins during the preparation process of molecularly imprinted polymers (MIPs) remains challenging. Ionic liquids (ILs), being capable of maintaining the stability of proteins, might enable effective imprinting and accurate recognition of proteins. In this study, lysozyme (Lyz)-imprinted titanium dioxide (TiO2) nanoparticles, TiO2@Lyz-MIPs, have been successfully prepared for selective recognition and separation of Lyz. This was achieved by the free radical polymerization of hydroxyethyl acrylate (HEA) and poly(ethylene glycol) dimethacrylate (PEGDMA) on polydopamine (PDA)-modified TiO2 nanoparticles using an IL, choline dihydrogen phosphate (chol dhp), as the stabilizer of Lyz. It was found that both PDA modification of TiO2 and the use of chol dhp as stabilizer improved the adsorption capacity of TiO2@Lyz-MIPs toward Lyz. When the concentration of HEA was 7 mg mL-1, the ratio of monomer to crosslinker was 20 : 1, and the concentration of chol dhp was 12.5 mg mL-1, the highest imprinting factor of 4.40 was achieved. TiO2@Lyz-MIPs exhibited relatively high adsorption capacity with the maximum adsorption capacity up to 120 mg g-1, which was more than four times higher than that of the non-imprinted polymers (NIPs) counterpart, TiO2@Lyz-NIPs. The adsorption rate of Lyz by TiO2@Lyz-MIPs was also much higher than that of TiO2@Lyz-NIPs. TiO2@Lyz-MIPs could successfully separate Lyz from diluted egg white, a complex mixture of proteins. Findings from this study indicate that effective recognition cavities toward Lyz were formed on the surface of Lyz-imprinted TiO2 nanoparticles prepared using IL as the template stabilizer. This approach may facilitate the development of MIPs for efficient protein recognition and separation.

Functions of FACT in Breaking the Nucleosome and Maintaining Its Integrity at the Single-Nucleosome Level.

The human FACT (facilitates chromatin transcription) complex, composed of two subunits SPT16 (Suppressor of Ty 16) and SSRP1 (Structure-specific recognition protein-1), plays essential roles in nucleosome remodeling. However, the molecular mechanism of FACT reorganizing the nucleosome still remains elusive. In this study, we demonstrate that FACT displays dual functions in destabilizing the nucleosome and maintaining the original histones and nucleosome integrity at the single-nucleosome level. We found that the subunit SSRP1 is responsible for maintenance of nucleosome integrity by holding the H3/H4 tetramer on DNA and promoting the deposition of the H2A/H2B dimer onto the nucleosome. In contrast, the large subunit SPT16 destabilizes the nucleosome structure by displacing the H2A/H2B dimers. Our findings provide mechanistic insights by which the two subunits of FACT coordinate with each other to fulfill its functions and suggest that FACT may play essential roles in preserving the original histones with epigenetic identity during transcription or DNA replication.

lncRNA PAPAS tethered to the rDNA enhancer recruits hypophosphorylated CHD4/NuRD to repress rRNA synthesis at elevated temperatures.

Attenuation of pre-rRNA synthesis in response to elevated temperature is accompanied by increased levels of PAPAS ("promoter and pre-rRNA antisense"), a long noncoding RNA (lncRNA) that is transcribed in an orientation antisense to pre-rRNA. Here we show that PAPAS interacts directly with DNA, forming a DNA-RNA triplex structure that tethers PAPAS to a stretch of purines within the enhancer region, thereby guiding associated CHD4/NuRD (nucleosome remodeling and deacetylation) to the rDNA promoter. Protein-RNA interaction experiments combined with RNA secondary structure mapping revealed that the N-terminal part of CHD4 interacts with an unstructured A-rich region in PAPAS. Deletion or mutation of this sequence abolishes the interaction with CHD4. Stress-dependent up-regulation of PAPAS is accompanied by dephosphorylation of CHD4 at three serine residues, which enhances the interaction of CHD4/NuRD with RNA and reinforces repression of rDNA transcription. The results emphasize the function of lncRNAs in guiding chromatin remodeling complexes to specific genomic loci and uncover a phosphorylation-dependent mechanism of CHD4/NuRD-mediated transcriptional regulation.

Resveratrol improves glucose uptake in insulin-resistant adipocytes via Sirt1.

Insulin resistance serves as "common soil" for promoting the development of metabolic diseases; however, the precise pathological factors leading to insulin resistance are not well clarified. Resveratrol (Res) is a natural polyphenolic compound with anti-inflammatory and antioxidative effects. However, effects and mechanisms of Res on glucose metabolism in adipocytes remain largely unknown. In this study, we show Res treatment significantly increases glucose uptake in insulin-resistant 3T3-L1 adipocytes in vitro. Mechanistically, Res up-regulates the protein level of Sirt1 that improves insulin signaling pathway and promotes cellular membrane Glut4 accumulation. Meanwhile, Sirt1 enhances phosphorylation level of AMPK which elevates p-AKT level. Consequently, the transcription factor FOXO1 translocalizes from nucleus to cytoplasm where protein degradation occurs. Therefore, the gene expression of resistin, a direct transcriptional target of FOXO1, is reduced and insulin sensitivity is improved. Importantly, we recapitulate the similar pattern of related protein changes in epididymal adipose tissues of insulin-resistant mice after Res intervention in vivo, reinforcing the hypothesis of Res being involved in regulation of glucose uptake via Sirt1-AMPK axis. Our findings clarify the beneficial effects of Res on glucose transportation in insulin-resistant adipocytes and involved pathway including Sirt1-AMPK, suggesting its potential therapeutic application in the treatment or prevention of insulin-resistance-related metabolic symptoms.

Nucleosome Positioning Assay.

The basic unit of chromatin is the nucleosome, a histone octamer with 147 base pairs of DNA wrapped around it. Positions of nucleosomes relative to each other and to DNA elements have a strong impact on chromatin structure and gene activity and are tightly regulated at multiple levels, i.e., DNA sequence, transcription factor binding, histone modifications and variants, and chromatin remodeling enzymes ( Bell et al., 2011 ; Hughes and Rando, 2014). Nucleosome positions in cells or isolated nuclei can be detected by partial nuclease digestion of native or cross-linked chromatin followed by ligation-mediated polymerase chain reaction (LM-PCR) ( McPherson et al., 1993 ; Soutoglou and Talianidis, 2002). This protocol describes a nucleosome positioning assay using Micrococcal Nuclease (MNase) digestion of formaldehyde-fixed chromatin followed by LM-PCR. We exemplify the nucleosome positioning assay for the promoter of genes encoding ribosomal RNA (rRNA genes or rDNA) in mice, which has two mutually exclusive configurations. The rDNA promoter harbors either an upstream nucleosome (NucU) covering nucleotides -157 to -2 relative to the transcription start site, or a downstream nucleosome (NucD) at position -132 to +22 ( Li et al., 2006 ; Xie et al., 2012 ). Radioactive labeling of LM-PCR products followed by denaturing urea-polyacrylamide gel electrophoresis allows resolution and relative quantification of both configurations. As depicted in the diagram in Figure 1, the nucleosome positioning assay is a versatile low to medium throughput method to map discrete nucleosome positions with high precision in a semi-quantitative manner. Figure 1.Flow chart depicting the nucleosome positioning assay. The diagram shows how the assay is used to detect the ratio between upstream (NucU) and downstream (NucD) nucleosome positions at the mouse rDNA promoter. After all steps have been performed, the LM-PCR yields two radiolabeled products that differ in size and correspond to NucU and NucD. Signal intensities of the bands reflect the relative abundance of each nucleosome position in the original sample.

Heat shock represses rRNA synthesis by inactivation of TIF-IA and lncRNA-dependent changes in nucleosome positioning.

Attenuation of ribosome biogenesis in suboptimal growth environments is crucial for cellular homeostasis and genetic integrity. Here, we show that shutdown of rRNA synthesis in response to elevated temperature is brought about by mechanisms that target both the RNA polymerase I (Pol I) transcription machinery and the epigenetic signature of the rDNA promoter. Upon heat shock, the basal transcription factor TIF-IA is inactivated by inhibition of CK2-dependent phosphorylations at Ser170/172. Attenuation of pre-rRNA synthesis in response to heat stress is accompanied by upregulation of PAPAS, a long non-coding RNA (lncRNA) that is transcribed in antisense orientation to pre-rRNA. PAPAS interacts with CHD4, the adenosine triphosphatase subunit of NuRD, leading to deacetylation of histones and movement of the promoter-bound nucleosome into a position that is refractory to transcription initiation. The results exemplify how stress-induced inactivation of TIF-IA and lncRNA-dependent changes of chromatin structure ensure repression of rRNA synthesis in response to thermo-stress.

lncRNA-Induced Nucleosome Repositioning Reinforces Transcriptional Repression of rRNA Genes upon Hypotonic Stress.

The activity of rRNA genes (rDNA) is regulated by pathways that target the transcription machinery or alter the epigenetic state of rDNA. Previous work has established that downregulation of rRNA synthesis in quiescent cells is accompanied by upregulation of PAPAS, a long noncoding RNA (lncRNA) that recruits the histone methyltransferase Suv4-20h2 to rDNA, thus triggering trimethylation of H4K20 (H4K20me3) and chromatin compaction. Here, we show that upregulation of PAPAS in response to hypoosmotic stress does not increase H4K20me3 because of Nedd4-dependent ubiquitinylation and proteasomal degradation of Suv4-20h2. Loss of Suv4-20h2 enables PAPAS to interact with CHD4, a subunit of the chromatin remodeling complex NuRD, which shifts the promoter-bound nucleosome into the transcriptional "off" position. Thus, PAPAS exerts a "stress-tailored" dual function in rDNA silencing, facilitating either Suv4-20h2-dependent chromatin compaction or NuRD-dependent changes in nucleosome positioning.

Human PIH1 associates with histone H4 to mediate the glucose-dependent enhancement of pre-rRNA synthesis.

Ribosome biogenesis is critical in the growth of eukaryotic cells, in which the synthesis of precursor ribosomal RNA is the first and rate-limiting step. Here, we show that human PIH1 domain-containing protein 1 (PIH1) interacts directly with histone H4 and recruits the Brg1-SWI/SNF complex via SNF5 to human rRNA genes. This process is likely involved in PIH1-dependent DNase I-hypersensitive chromatin remodeling at the core promoter of the rRNA genes. PIH1 mediates the occupancy of not only the Brg1 complex but also the Pol I complex at the core promoter and enhances transcription initiation of rRNA genes. Additionally, the interaction between PIH1 and H4K16 expels TIP5, a component of the silencing nucleolar remodeling complex (NoRC), from the core region, suggesting that PIH1 is involved in the derepression of NoRC-silenced rRNA genes. These data indicate that PIH1 is a positive regulator of human rRNA genes and is of great importance for the recovery of human cells from nutrient starvation and the transition to glucose-induced exponential growth in vivo.

Apoptosis related protein 3, an ATRA-upregulated membrane protein arrests the cell cycle at G1/S phase by decreasing the expression of cyclin D1.

Human Apr3 was first cloned from HL-60 cells treated by ATRA. In this study, we further demonstrated that Apr3 could be obviously upregulated by ATRA in many other ATRA sensitive cells, suggesting a common role of Apr3 in ATRA effects. Indirect immunofluorescence assay indicates that Apr3 is a membrane protein, while its truncated form without the predicted transmembrane and intracellular domain, was likely a secreted one. Furthermore, FACS analysis showed that Apr3 overexpression could cause an obvious G1/S phase arrest which might be induced by dramatic reduction of cyclin D1 expression. Strikingly, the truncated Apr3 antagonized the negative role of Apr3 on cell cycle and cyclin D1. Taken together, our data suggest that Apr3 should play an important role in ATRA signal pathway and the predicted transmembrane and/or the intracellular domain mediates Apr3 membrane localization and is vital for the negative regulation on cell cycle and cyclin D1.

Identification of the distinct promoters for the two transcripts of apoptosis related protein 3 and their transcriptional regulation by NFAT and NFkappaB.

APR3 (apoptosis related protein 3) is a novel gene highly conserved across species. Analysis of the data about APR3 available at GEO profiles revealed consistent and significant changes of APR3 expression level in certain developmental and inflammatory processes. Based on the search and analysis of all the submitted mRNA sequence, we postulated that the two transcripts may arise from separate promoter activities rather than previously assumed alternative splicing. Through reporter assay and PCR data, we identified the distinct promoters for the two transcripts of APR3. Furthermore, exogenous expression of a constitutively active mutant of transcription factor NFAT was able to enhance both the promoter activities of APR3. Sequential deletion of the promoter from the 5' side and mutation of the promoter suggested the functional NFAT binding sites might localize between -96 bp and -47 bp. In contrast, exogenous expression of a constitutively active mutant of the transcription factor NFkB inhibited APR3 transcription. Our data suggested that APR3 might be functionally important in certain processes under which NFAT and/or NFkappaB are/is activated.

Transcriptional upregulation of restin by p53.

Restin, belonging to the melanoma-associated antigen superfamily, was firstly cloned from the differentiated HL-60 cells when induced by all-trans retinoic acid (ATRA) in our lab. Our previous results showed that restin might be correlated to cell cycle arrest. Due to the importance of p53 in the regulation of cell growth and the relationship between p53 and ATRA, we tried to test the relationship between p53 and restin. Firstly, transfection results showed that p53 was able to upregulate the expression of restin at the transcriptional level when p53 was transfected into eukaryotic cells. Secondly, the bioinformatics analysis revealed that the upstream sequence (about 2 kb) from the first ATG of the ORF of restin gene contained a p53 binding site. In order to confirm that p53 was involved in the transcriptional regulation of restin, we cloned the upstream sequence of restin and constructed the promoter luciferase reporter system. From the luciferase activity, we demonstrated that the promoter of restin gene could be induced by ATRA. Then, another two luciferase reporter plasmids driven by the reporter of restin with no (RPdelta p53-luc) or mutant (mRP-luc) p53 binding site were constructed to see the regulation of restin by p53. Results showed that the transcriptional upregulation of restin gene was not due to the putative p53 binding site on the upstream of restin gene. We proposed that p53 upregulated restin transcription through an indirect way rather than direct interaction with the cis-activating element of the restin promoter.

[Cloning and characterization of genes differentially expressed in human dental pulp cells and gingival fibroblasts].

OBJECTIVE: To study the biological properties of human dental pulp cells (HDPC) by cloning and analysis of genes differentially expressed in HDPC in comparison with human gingival fibroblasts (HGF). METHODS: HDPC and HGF were cultured and identified by immunocytochemistry. HPDC and HGF subtractive cDNA library was established by PCR-based modified subtractive hybridization, genes differentially expressed by HPDC were cloned, sequenced and compared to find homogeneous sequence in GenBank by BLAST. RESULTS: Cloning and sequencing analysis indicate 12 genes differentially expressed were obtained, in which two were unknown genes. Among the 10 known genes, 4 were related to signal transduction, 2 were related to trans-membrane transportation (both cell membrane and nuclear membrane), and 2 were related to RNA splicing mechanisms. CONCLUSION: The biological properties of HPDC are determined by the differential expression of some genes and the growth and differentiation of HPDC are associated to the dynamic protein synthesis and secretion activities of the cell.

Genetic structure of Przewalski's rock partridge (Alectoris magna) populations in the Longzhong Loess Plateau, China.

In this paper, we have analyzed the nuclear DNA of Alectoris magna samples, collected from the Longzhong Loess Plateau. We used allelic variation at eight microsatellite markers to describe the genetic structure of A. magna populations. The primary goal of this study was to examine the population genetic structure and determine the extent of population differentiation among populations of A. magna. The average value of H(E) (0.455) was smaller than H(O) (0.477), and there was a heterozygote deficit at the MCW135 locus in the Lanzhou population and the Beidao population. The AB063167 locus in each population (except that of Jingyuan) was not in equilibrium (P < 0.05). The Lixian edge population had a lower proportion of genetic diversity than the central geographic populations; the Haiyuan and Jingyuan populations had higher genetic diversity than the central geographic populations. Analysis of population structure revealed clear differentiation among the eight populations of A. magna, suggesting strong isolation of these populations and correspondingly low levels of migration or gene flow. The A. magna populations of Longzhong Loess Plateau are separated into eastern and western populations by a clustering chart. Genetic data indeed suggest that patterns of speciation and population diversification of A. magna in the Longzhong Plateau have been affected by the stability of the climate, natural selection, and human intervention.

COOH-terminal Src kinase-mediated c-Jun phosphorylation promotes c-Jun degradation and inhibits cell transformation.

The oncoprotein c-Jun is a component of the activator protein-1 transcription factor complex, which is involved in cellular proliferation, transformation, and death. The stabilization of c-Jun is critically important for its function. The phosphorylation of c-Jun by c-Jun NH(2)-terminal kinase 1 and extracellular signal-regulated protein kinases reduces c-Jun ubiquitination resulting in increased stabilization of c-Jun. In this report, we showed that COOH-terminal Src kinase (CSK) binds with and phosphorylates c-Jun at Y26 and Y170. Phosphorylation of c-Jun by CSK, in opposition to c-Jun NH(2)-terminal kinase 1 and extracellular signal-regulated protein kinases, promoted c-Jun degradation and reduced stability. By promoting c-Jun degradation, CSK helps to maintain a low steady-state level of c-Jun, thereby inhibiting activator protein-1 activity and cell transformation caused by c-Jun. These results indicated that this function of CSK controls cell proliferation under normal growth conditions and may have implications for CSK loss of function in carcinogenesis.