Jun Zhu

Shanghai Jiao Tong University, Shanghai, Shanghai Shi, China

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Publications (29)300.64 Total impact

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    ABSTRACT: PML/RARA is the oncoprotein driving acute promyelocytic leukemia (APL). It suppresses genes expression by recruitment of a number of transcriptional repressors, resulting in differentiation block and malignant transformation of hematopoietic cells. Here, we found that mice primary hematopoietic progenitor cells (HPCs), transduced by DNA-binding-defective PML/RARA mutants, were deficient in colony formation. Further experiments showed that DNA-binding-defective PML/RARA mutants could not repress the transcription of retinoic acid regulated genes. Intriguingly, there were no significant differences of the micro-speckled intracellular distribution between the mutants and wild-type PML/RARA. Some retinoic acid target genes regulated by PML/RARA are involved in not only differentiation block but also hematopoietic cell self-renewal. Altogether, our data demonstrate that direct DNA-binding is essential for PML/RARA to immortalize hematopoietic cells, while disruption of PML-nuclear body does not seem to be a prerequisite for hematopoietic cell transformation.
    PLoS ONE 01/2014; 9(8):e104906. · 3.53 Impact Factor
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    ABSTRACT: The relative genetic simplicity of leukaemias, the development of which likely relies on a limited number of initiating events has made them ideal for disease modelling, particularly in the mouse. Animal models provide incomparable insights into the mechanisms of leukaemia development and allow exploration of the molecular pillars of disease maintenance, an aspect often biased in cell lines or ex vivo systems. Several of these models, which faithfully recapitulate the characteristics of the human disease, have been used for pre-clinical purposes and have been instrumental in predicting therapy response in patients. We plea for a wider use of genetically defined animal models in the design of clinical trials, with a particular focus on reassessment of existing cancer or non-cancer drugs, alone or in combination.
    Molecular oncology 02/2013; · 6.70 Impact Factor
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    ABSTRACT: In(OH)3 nanomaterials with different morphologies or hierarchical structures, such as nanoparticles, monodispersed hierarchical nanocubes and nanospheres, have been successfully synthesized via a ligand-assisted aqueous process. The shape and size of these as-prepared architectures can be tuned effectively by controlling the reaction conditions, such as the molar ratio of ligand/In3+ and different ligands. Further studies reveal that both Na3cit and urea are necessary for the formation of monodispersed hierarchical nanospheres and nanocubes. Furthermore, In2O3 nanoparticles and monodispersed hierarchical nanocubes and nanospheres with well-defined morphologies of the precursors can be also obtained by annealing the corresponding In(OH)3 samples. The gas sensing properties of the as-prepared In2O3 samples demonstrate that hierarchical In2O3 architectures exhibit a superior response to ethanol gas, and the hierarchical In2O3 nanocubes have excellent selectivity and sensitivity. Further more, XPS spectra and N2 adsorption-desorption isotherms achieve a deeper understanding of the effects of the final product morphologies on their gas sensing properties.
    Journal of Materials Chemistry 01/2013; 1(3):735-745. · 6.63 Impact Factor
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    ABSTRACT: The regulation of hematopoiesis is generally evolutionarily conserved from zebrafish to mammals, including hematopoietic stem cell formation and blood cell lineage differentiation. In zebrafish, primitive granulocytes originate at two distinct regions, the anterior lateral plate mesoderm (A-LPM) and the intermediate cell mass (ICM). Few studies in the zebrafish have examined genes specifically required for the granulocytic lineage. In this study, we identified the responsible gene for a zebrafish mutant that has relatively normal hematopoiesis, except decreased expression of the granulocyte-specific gene mpx. Positional cloning revealed that phospholipase C gamma-1 (plcg1) was mutated. Deficiency of plcg1 function specifically affected development of granulocytes, especially the maturation process. These results suggested that plcg1 functioned specifically in zebrafish ICM granulopoiesis for the first time. Our studies suggest that specific pathways regulate the differentiation of the hematopoietic lineages.
    Developmental Biology 12/2012; · 3.87 Impact Factor
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    ABSTRACT: To establish the model of hepatic fibrosis in mice infected with Schistosoma japonicum and observe the expression of transforming growth factor-beta1 (TGF-beta1) and connective tissue growing factor (CTGF) in mice model. Thirty BALB/c mice were randomly assigned to control group and model group. Each mouse of model group was infected with (30 +/- 1) S. japonicum cercariae through the abdominal skin. Serum samples were collected at 4, 6, 8, 10, and 12 weeks after infection, and were analyzed for the levels of ALT and AST. Pathological changes and proliferation of hepatic collagen fibers in liver tissue were observed after HE staining and Masson staining. Immunohistochemistry and real-time PCR were used to detect the protein and mRNA expression of CTGF and TGF-pl. 6-12 weeks after infection, there was significant difference in ALT and AST between model group and control group (P43.05). At 12th week, ALT [(173.53 +/- 31.12) U/I] and AST [(301.00 +/- 34.87) U/LI in model group were higher than those in control group [(42.00 +/- 3.53) and 96.58 +/- 11.26) U/L] . In model group, egg granulomas formed in the liver, and the formation of hepatic fibrosis was significant in portal areas, and tbere was tree-like hepatic fibrosis around the portal vein branch. 8 weeks after infection, hepatic fibrosis area in mice of model group increased considerably, and there was significant difference in percentage of positive area of collagen between 12th week [(23.83 +/- 1.68) %] and control group [(1.23 +/- 0.14) %] (P < 0.05). 10 and 12 weeks after infection, the percentage of positive area of TGF-beta1 [(22.34 +/- 2.58)% and (25.82 +/- 3.01) %] and CTGF [(1 l.32 +/- 2.44)% and (14.51 +/- 2.05) %] was higher respectively than that of the control [(2.56 +/- 0.87)%, and (1.09 +/- 0.73)% (P < 0.05). 6, 8, 10, and 12 weeks after infection, both TGF-beta1 and CTGF mRNA increased gradually, higher than that in control group (P < 0.05). 10 weeks after infection, TGF-beta1 mRNA relative transcription level was the highest (0.0721 +/- 0.0187) and it was 0.0089 +/- 0.0037 in control group. CTGF mRNA relative transcription level reached the highest value (0.1136 +/- 0.0365) in 12 weeks after infection, while it was 0.0293 +/- 0.0184 in control group. CTGF mRNA expression was positively correlated with the duration of infection (r = 0.927, NO.05). The area and cell types of TGFp1 positive expression is the same as that of CTGF in liver tissue of schistosome4nfected mice (BALE/c). CTGF mRNA expression is significantly related to the duration of infection, but it is not the case for TGF-pl.
    Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases 02/2012; 30(1):20-6.
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    ABSTRACT: Acute promyelocytic leukemia (APL) is a hematological malignancy driven by the PML/RARA oncogene. The prognosis for patients with APL was revolutionized by two treatments: retinoic acid (RA) and As(2)O(3) (arsenic trioxide). These were both shown a posteriori to target PML/RARA, explaining their exquisite specificity for APL. Arsenic, as a single agent, cures up to 70% of patients, whereas APL patients treated with the combination of RA and As(2)O(3) reach a stunning 90% cure rate. Recent physiopathological models highlight the key role of RA- and As(2)O(3)-triggered PML/RARA degradation, and the molecular mechanisms underlying As(2)O(3)-induced PML/RARA degradation have been recently clarified. As discussed below, arsenic binding, oxidation, sumoylation on PML nuclear bodies, and RNF4-mediated ubiquitination all contribute to the As(2)O(3)-triggered catabolism of PML/RARA.
    Trends in Molecular Medicine 11/2011; 18(1):36-42. · 9.57 Impact Factor
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    ABSTRACT: Hematopoiesis is evolutionarily conserved from zebrafish to mammals, and this includes both primitive and definitive waves during embryogenesis. Primitive hematopoiesis is dominated by erythropoiesis with limited myelopoiesis. Protein sumoylation, a ubiquitination-like posttranslational protein modification, is implicated in a variety of biochemical processes, most notably in transcriptional repression. We show here that the loss of 6 small ubiquitin-related modifier (SUMO) paralogs triggers a sharp up-regulation of the myeloid-specific marker mpo and down-regulation of the erythroid-specific marker gata1 in myelo-erythroid progenitor cells (MPCs) in the intermediate cell mass (ICM) during primitive hematopoiesis. Accordingly, in transgenic zebrafish lines, hyposumoylation expands myelopoiesis at the expense of erythropoiesis. A SUMO-CCAAT/enhancer-binding protein α (SUMO-C/ebpα) fusion restores the normal myelopoiesis/erythropoiesis balance, suggesting that sumoylation status of C/ebpα contributes to myelo-erythroid lineage determination. Our results therefore implicate sumoylation in early lineage determination and reveal the possible molecular mechanism underlying the puzzling biased primitive hematopoiesis in vertebrates.
    Blood 05/2011; 117(26):7014-20. · 9.78 Impact Factor
  • Jun Zhu, Xuefeng Qian
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    ABSTRACT: Assembled ZnQ2·2H2O microstructures, such as microsheet, sandwich-like structure and hexangular microflake, have been successfully prepared in CTAB microemulsion system through the stacking of ZnQ2·2H2O molecules and oriented aggregation of ZnQ2·2H2O original building blocks. Controlled experiments demonstrated that the morphologies of building block and final product could be readily tuned by reaction parameters, and a formation mechanism, involving re-precipitation, growth and oriented aggregation process, has been proposed on the basis of time-dependent experimental results. The obtained products were carefully characterized by X-ray powder diffraction (XRD), thermal gravimetric analysis (TGA), transmission electron microscope (TEM), field-emission scanning electron microscope (FESEM), FT-IR spectrum, UV–vis spectrum and photoluminescence (PL) spectrum. The surface photovoltage (SPV) of the obtained ZnQ2·2H2O microstructures was investigated by means of surface photovoltage spectroscopy (SPS) and field-induced surface photovoltage spectroscopy (FISPS). The SPS and FISPS revealed that the photogenerated charges of ZnQ2·2H2O could be separated distinctly and ZnQ2·2H2O possessed p-type semiconductor characteristics, respectively. Furthermore, UV–vis and PL spectra evidenced the optical properties of ZnQ2·2H2O were sensitive to its microstructure or morphology.
    Solid State Sciences 08/2010; 12(8):1314–1322. · 1.67 Impact Factor
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    ABSTRACT: Three-dimensional (3D) hierarchical Bi2WO6 microspheres were successfully synthesized by a simple inorganic salt-assisted hydrothermal process. Morphology modulation of the obtained products could be easily realized by tuning the concentration of the nitrate. It is worthy to note that the obtained hierarchical Bi2WO6 microspheres exhibit powerful visible-light-photocatalytic activity for the degradation of Rhodamine-B (RhB) under 300 W Xe lamp light irradiation. A possible salt-assisted formation mechanism was proposed on the basis of the experimental results. Furthermore, this work might represent a novel synthesis strategy for other photocatalysts with desired photocatalytic activity.
    CrystEngComm 01/2010; 12(7). · 3.88 Impact Factor
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    ABSTRACT: Acute promyelocytic leukemia (APL) is characterized by a specific t(15;17) chromosomal translocation that yields the PML/RARA fusion gene. Clinically, besides chemotherapy, two drugs induce clinical remissions: retinoic acid (RA) and arsenic trioxide (As). Both agents directly target PML/RARA-mediated transcriptional repression and protein stability, inducing to various extent promyelocyte differentiation and clinical remission of APL patients. RA targets the RARA moiety of the fusion, whereas arsenic targets its PML part. PML/RARA expression in the mouse is sufficient to initiate APL. The RA-As association, which synergizes for PML/RARA degradation but not for differentiation, rapidly clears leukemia initiating cells (LIC), resulting in APL eradication in murine APL models, but also in several APL clinical trials. Cyclic AMP triggered PML/RARA phosphorylation also enhances RA-induced APL regression, PML/RARA degradation, and LIC clearance, raising new options for therapy-resistant patients. Although differentiation has a major role in debulking of the tumor, PML/RARA degradation seems to be the primary basis for APL eradication by the RA-As association. Oncoprotein degradation could be a general therapeutic strategy that may be extended beyond APL.
    Clinical Cancer Research 10/2009; 15(20):6321-6. · 7.84 Impact Factor
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    ABSTRACT: The Small ubiquitin-related modifier (SUMO) conjugation to a variety of proteins regulates diverse cellular processes, including transcription, cell cycle regulation and maintenance of genome integrity. To investigate in vivo biological function of SUMO paralogs, we inactivated them in the early development of zebrafish. While zebrafish embryos deficient for all three SUMO paralogs, as Ubc9-deficient ones, displayed severe defects, loss of individual SUMO paralog was compatible with a normal development. SUMO-deficient embryos can be rescued by a single human or zebrafish SUMO. While key structural basic lysine residues and N-terminal unstructured stretch of SUMO are critical for in vivo rescue, the consensus K11 sumoylation site of SUMO2 is dispensable, implying that chain formation on this potential site is unessential for normal development. Inactivation of all three SUMOs triggered p53-dependent apoptosis and further inactivation of p53 restored normal zebrafish development. Interestingly, we also demonstrate that the dominant negative truncated form of p53, Delta113p53, significantly blunts SUMO depletion-induced p53 activity in vivo. Taken together, our results suggest that SUMO paralogs are indispensable, but redundant, in the early development of zebrafish.
    Cell Research 09/2009; 20(2):185-96. · 10.53 Impact Factor
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    ABSTRACT: Cubic-like CeO2 nanocrystals were successfully synthesized through an improved-toluene solvothermal process using hexadecylamine (HAD) as a capping agent and CeCl3·7H2O as a precursor at 180 °C for 24 h. These nanocubes are about 10 nm in size, and have a tendency to assemble into 2D superstructure. The obtained samples were characterized by means of X-ray powder diffraction (XRD) and transmission electron microscopy (TEM). It was found that the water content, the concentration of ligand and kinds of aliphatic amine played important roles in the formation of the novel morphology. A possible formation mechanism was proposed based on the controlling reaction parameters. The electrochemical and photocatalytic properties of the as-synthesized samples exhibited the size/shape-dependent properties and potential applications.
    Materials Chemistry and Physics. 01/2009;
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    ABSTRACT: Yttrium fluoride such as Na(Y1.5Na0.5)F6 and α-NaYF4; YF3 has been successfully synthesized via a salt-assisted hydrothermal method in the presence of sodium nitrate. The morphology and chemical composition of the as-obtained products can be controlled by monitoring the reaction parameters inclusive of the time-zero concentration of salt solution, reaction temperature and time. The as-prepared products cover Na(Y1.5Na0.5)F6, α-NaYF4 and YF3, while the corresponding morphology changes from spherical aggregation to octahedron, which were characterized by XRD, SEM, and TEM. Moreover, LnF3 (Ln = La, Nd, Eu, Gd) can also be synthesized using the same method. Further studies reveal that the morphology and composition of the as-synthesized lanthanide fluoride can be determined mainly by the ionic radius of rare earth and the concentration of NaNO 3. It is emphasized that the sodium nitrate plays an important role in such control of the differentiated products. Apart from these findings, the photoluminescent properties of Eu3+:YF3 octahedral crystals are further investigated. © The Royal Society of Chemistry.
    CrystEngComm 01/2009; 12(1):199-206. · 3.88 Impact Factor
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    ABSTRACT: Nearly monodisperse YVO(4) architectures with persimmon-like, cube-like and nanoparticle shapes have been synthesised on a large scale by means of a complexing-agent-assisted solution route. The shape and size of these as-prepared architectures can be tuned effectively by controlling the reaction conditions, such as reaction time, the molar ratio of complexing agent/Y(3+) and different complexing agents. As a typical morphology, the growth process of monodisperse nanopersimmons has been examined. To extend this method, other LnVO(4) (Ln=Ce, Gd, Dy, Er) complexes with well-defined shape and dimensionality can also be achieved by adjusting different rare earth precursors. Further studies reveal that the morphology of the as-synthesised lanthanide orthovanadate is determined mainly by the interaction between rare earth ion and the complexing agent. Ultraviolet (UV) absorption and photoluminescence spectra show that the optical properties of YVO(4) nanopersimmons are relevant to their size and shape. This work sheds some light on the design of well-defined complex nanostructures, and explores the potential applications of the as-synthesised architectures.
    Chemistry - A European Journal 12/2008; 15(5):1233 - 1240. · 5.93 Impact Factor
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    ABSTRACT: Retinoic acid and arsenic trioxide target the protein stability and transcriptional repression activity of the fusion oncoprotein PML-RARA, resulting in regression of acute promyelocytic leukemia (APL). Phenotypically, retinoic acid induces differentiation of APL cells. Here we show that retinoic acid also triggers growth arrest of leukemia-initiating cells (LICs) ex vivo and their clearance in PML-RARA mouse APL in vivo. Retinoic acid treatment of mouse APLs expressing the fusion protein PLZF-RARA triggers full differentiation, but not LIC loss or disease remission, establishing that differentiation and LIC loss can be uncoupled. Although retinoic acid and arsenic synergize to clear LICs through cooperative PML-RARA degradation, this combination does not enhance differentiation. A cyclic AMP (cAMP)-dependent phosphorylation site in PML-RARA is crucial for retinoic acid-induced PML-RARA degradation and LIC clearance. Moreover, activation of cAMP signaling enhances LIC loss by retinoic acid, identifying cAMP as another potential APL therapy. Thus, whereas transcriptional activation of PML-RARA is likely to control differentiation, its catabolism triggers LIC eradication and long-term remission of mouse APL. Therapy-triggered degradation of oncoproteins could be a general strategy to eradicate cancer stem cells.
    Nature medicine 12/2008; 14(12):1333-42. · 27.14 Impact Factor
  • Jun Zhu, Xuefeng Qian
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    ABSTRACT: Ultra-long and flexible necklace-like nanostructures of cadmium hydroxide were successfully prepared in the n-octanol/aqueous liquid system through the microwave heating approach, and a novel mechanism based on the synergistic effect of bubble-template and interface-assistance (SEBI) was proposed. The obtained products were carefully characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), field-emission scanning electron microscopy (FESEM), FT-IR spectrum, UV–vis adsorption spectrum and BET measurement. Control experiments revealed that the morphologies of the building blocks and the final products could be readily tuned by the reaction parameters. Further experiments evidenced that the positively charged Cd(OH)2 could effectively adsorb or separate the negatively charged dye molecules, and the hierarchical structure could improve its separation performance.
    Solid State Sciences 11/2008; 10(11):1577-1583. · 1.67 Impact Factor
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    ABSTRACT: In acute promyelocytic leukaemia (APL), arsenic trioxide induces degradation of the fusion protein encoded by the PML-RARA oncogene, differentiation of leukaemic cells and produces clinical remissions. SUMOylation of its PML moiety was previously implicated, but the nature of the degradation pathway involved and the role of PML-RARalpha catabolism in the response to therapy have both remained elusive. Here, we demonstrate that arsenic-induced PML SUMOylation triggers its Lys 48-linked polyubiquitination and proteasome-dependent degradation. When exposed to arsenic, SUMOylated PML recruits RNF4, the human orthologue of the yeast SUMO-dependent E3 ubiquitin-ligase, as well as ubiquitin and proteasomes onto PML nuclear bodies. Arsenic-induced differentiation is impaired in cells transformed by a non-degradable PML-RARalpha SUMOylation mutant or in APL cells transduced with a dominant-negative RNF4, directly implicating PML-RARalpha catabolism in the therapeutic response. We thus identify PML as the first protein degraded by SUMO-dependent polyubiquitination. As PML SUMOylation recruits not only RNF4, ubiquitin and proteasomes, but also many SUMOylated proteins onto PML nuclear bodies, these domains could physically integrate the SUMOylation, ubiquitination and degradation pathways.
    Nature Cell Biology 06/2008; 10(5):547-55. · 20.76 Impact Factor
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    ABSTRACT: Ultrathin β-In2S3 nanobelts have been successfully synthesized via a facile improved solvothermal route. The crystal phase, morphology, crystal lattice and composition of as-prepared products were characterized by XRD, FESEM, TEM, HRTEM and EDS, respectively. Results revealed that the as-synthesized β-In2S3 nanobelts are in cubic structure 50−90 nm in width, 13 ± 2 nm in thickness, and the overall length even up to several microns. A possible shape evolution and crystal growth mechanism was suggested, and the formation of β-In2S3 nanobelts resulted from the preferential growth along the 220 direction and enclosed by {202} and {022̅} crystallographic facets. The strong quantum confinement effect in UV−vis spectra and the blue emission in photoluminescence spectra imply the as-synthesized β-In2S3 nanobelts as a promising candidate for phosphor in display devices. Furthermore, the good photocatalytic effects indicate that these β-In2S3 nanobelts are likely to be applied as a new kind of photocatalyst in the future.
    Crystal Growth & Design - CRYST GROWTH DES. 01/2008; 8(7):2130-2136.
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    ABSTRACT: Although PML-enforced RARA homodimerization allows PML/RARA to bind DNA independently of its coreceptor RXR, the latter was identified within the PML/RARA complex. We demonstrate that a PML/RARA mutant defective for RXR binding fails to trigger APL development in transgenic mice, although it still transforms primary hematopoietic progenitors ex vivo. RXR enhances PML/RARA binding to DNA and is required for rexinoid-induced APL differentiation. In RA-treated PML/RARA-transformed cells, the absence of RXR binding results in monocytic, rather than granulocytic, differentiation. PML/RARA enhances posttranslational modifications of RXRA, including its sumoylation, suggesting that PML-bound sumoylation enzymes target RXRA and possibly other PML/RARA-bound chromatin proteins, further contributing to deregulated transcription. Thus, unexpectedly, RXR contributes to several critical aspects of in vivo transformation.
    Cancer Cell 08/2007; 12(1):23-35. · 24.76 Impact Factor
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    ABSTRACT: Promyelocytic leukemia (PML) has been implicated in a variety of functions, including control of TP53 function and modulation of cellular senescence. Sumolated PML is the organizer of mature PML bodies, recruiting a variety of proteins onto these nuclear domains. The PML gene is predicted to encode a variety of protein isoforms. Overexpression of only one of them, PML-IV, promotes senescence in human diploid fibroblasts, whereas PML-III was proposed to specifically interact with the centrosome. We show that all PML isoform proteins are expressed in cell lines or primary cells. Unexpectedly, we found that PML-III, PML-IV, and PML-V are quantitatively minor isoforms compared with PML-I/II and could not confirm the centrosomal targeting of PML-III. Stable expression of each isoform, in a pml-null background, yields distinct subcellular localization patterns, suggesting that, like in other RBCC/TRIM proteins, the COOH-terminal domains of PML are involved in interactions with specific cellular components. Only the isoform-specific sequences of PML-I and PML-V are highly conserved between man and mouse. That PML-I contains all conserved exons and is more abundantly expressed than PML-IV suggests that it is a critical contributor to PML function(s).
    Cancer Research 07/2006; 66(12):6192-8. · 8.65 Impact Factor

Publication Stats

1k Citations
300.64 Total Impact Points

Institutions

  • 2008–2014
    • Shanghai Jiao Tong University
      • State Key Laboratory of Metal Matrix Composites
      Shanghai, Shanghai Shi, China
  • 2009–2013
    • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      Shanghai, Shanghai Shi, China
    • American University of Beirut
      • Department of Internal Medicine
      Beirut, Mohafazat Beyrouth, Lebanon
  • 2012
    • Shanghai Institute of Technology
      Shanghai, Shanghai Shi, China
  • 2011
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 2001–2006
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2002
    • La Ligue contre le cancer
      Lutetia Parisorum, Île-de-France, France