Bio

Professional Education


  • Bachelor of Science, National Taiwan University (1999)
  • Master of Science, National Taiwan University (2001)
  • Doctor of Philosophy, National Defense Medical Center (2010)

Stanford Advisors


Publications

Journal Articles


  • Epigenetic Roles of MLL Oncoproteins Are Dependent on NF-?B. Cancer cell Kuo, H., Wang, Z., Lee, D., Iwasaki, M., Duque-Afonso, J., Wong, S. H., Lin, C., Figueroa, M. E., Su, J., Lemischka, I. R., Cleary, M. L. 2013; 24 (4): 423-437

    Abstract

    MLL fusion proteins in leukemia induce aberrant transcriptional elongation and associated chromatin perturbations; however, the upstream signaling pathways and activators that recruit or retain MLL oncoproteins at initiated promoters are unknown. Through functional and comparative genomic studies, we identified an essential role for NF-κB signaling in MLL leukemia. Suppression of NF-κB led to robust antileukemia effects that phenocopied loss of functional MLL oncoprotein or associated epigenetic cofactors. The NF-κB subunit RELA occupies promoter regions of crucial MLL target genes and sustains the MLL-dependent leukemia stem cell program. IKK/NF-κB signaling is required for wild-type and fusion MLL protein retention and maintenance of associated histone modifications, providing a molecular rationale for enhanced efficacy in therapeutic targeting of this pathway in MLL leukemias.

    View details for DOI 10.1016/j.ccr.2013.08.019

    View details for PubMedID 24054986

  • Structural and Functional Roles of Daxx SIM Phosphorylation in SUMO Para log-Selective Binding and Apoptosis Modulation MOLECULAR CELL Chang, C., Naik, M. T., Huang, Y., Jeng, J., Liao, P., Kuo, H., Ho, C., Hsieh, Y., Lin, C., Huang, N., Naik, N. M., Kung, C. C., Lin, S., Chen, R., Chang, K., Huang, T., Shih, H. 2011; 42 (1): 62-74

    Abstract

    Small ubiquitin-like modifier (SUMO) conjugation and interaction are increasingly associated with various cellular processes. However, little is known about the cellular signaling mechanisms that regulate proteins for distinct SUMO paralog conjugation and interactions. Using the transcriptional coregulator Daxx as a model, we show that SUMO paralog-selective binding and conjugation are regulated by phosphorylation of the Daxx SUMO-interacting motif (SIM). NMR structural studies show that Daxx (732)E-I-I-V-L-S-D-S-D(740) is a bona fide SIM that binds to SUMO-1 in a parallel orientation. Daxx-SIM is phosphorylated by CK2 kinase at residues S737 and S739. Phosphorylation promotes Daxx-SIM binding affinity toward SUMO-1 over SUMO-2/3, causing Daxx preference for SUMO-1 conjugation and interaction with SUMO-1-modified factors. Furthermore, Daxx-SIM phosphorylation enhances Daxx to sensitize stress-induced cell apoptosis via antiapoptotic gene repression. Our findings provide structural insights into the Daxx-SIM:SUMO-1 complex, a model of SIM phosphorylation-enhanced SUMO paralog-selective modification and interaction, and phosphorylation-regulated Daxx function in apoptosis.

    View details for DOI 10.1016/j.molcel.2011.02.022

    View details for Web of Science ID 000289500500008

    View details for PubMedID 21474068

  • Clathrin heavy chain mediates TACC3 targeting to mitotic spindles to ensure spindle stability JOURNAL OF CELL BIOLOGY Lin, C., Hu, C., Shih, H. 2010; 189 (7): 1097-1105

    Abstract

    Mitotic spindles play essential roles in chromosome congression and segregation during mitosis. Aurora A regulates spindle assembly in part via phosphorylating human TACC3 on S558, which triggers TACC3 relocalization to mitotic spindles and stabilizes microtubules (MTs). In this study, we identified clathrin heavy chain (CHC) as an adaptor protein to recruit S558-phosphorylated TACC3 onto the spindle during mitosis for MT stabilization. CHC binds phospho-S558 TACC3 via its linker domain and first CHC repeat. CHC depletion or mutation on phospho-TACC3 binding abrogates TACC3 spindle relocalization. Depletion of either or both CHC and TACC3 yields similar defective phenotypes: loss of ch-TOG on spindles, disorganized spindles, and chromosome misalignment with comparable mitotic delay. Our findings elucidate the association between aurora A phosphorylation and spindle apparatus and demonstrate that regulation from aurora A is mediated by CHC in recruiting phospho-TACC3 and subsequently ch-TOG to mitotic spindles.

    View details for DOI 10.1083/jcb.200911120

    View details for Web of Science ID 000279188400008

    View details for PubMedID 20566684

  • Cdh1 controls the stability of TACC3. Cell cycle Jeng, J., Lin, Y., Lin, C., Shih, H. 2009; 8 (21): 3529-3536

    Abstract

    Transforming acidic coiled-coil protein 3 (TACC3) was reported to be important for regulating mitotic spindle assembly and chromosome segregation. While the protein level of TACC3 was shown to be altered during cell cycle progression, the molecular mechanism in controlling TACC3 level is unclear. Here, we show that TACC3 protein level can be regulated by Cdh1, a well known activator of anaphase-promoting complex/cyclosome. We identified Cdh1 as an interacting partner of TACC3 by a yeast array screen. Both in vitro and in vivo binding studies indicated that TACC3 can form complexes with Cdh1. Depletion of endogenous Cdh1 prolonged TACC3 protein level during mitotic exit. Alteration of Cdh1 level by ectopic overexpression or siRNA knockdown correlated well with an increase or decrease of ubiquitinated TACC3, respectively. Furthermore, the domain mapping studies of TACC3 revealed that multiple domains are involved in Cdh1-regulated degradation of TACC3. Altogether, our findings suggest that Cdh1 controls TACC3 protein stability during mitotic exit.

    View details for PubMedID 19823035

  • Molecular characterization and expression of four cDNAs encoding sucrose synthase from green bamboo Bambusa oldhamii NEW PHYTOLOGIST Chiu, W. B., Lin, C. H., Chang, C. J., Hsieh, M. H., Wang, A. Y. 2006; 170 (1): 53-63

    Abstract

    Bamboo is distinguished by its rapid growth. To investigate sucrose metabolism in this plant, we cloned the cDNAs encoding sucrose synthase (SuS) from Bambusa oldhamii and investigated their expression in growing shoots and leaves. Four cDNA clones, BoSus1, BoSus2, BoSus3 and BoSus4, were isolated by screening a cDNA library from etiolated bamboo shoots. Recombinant BoSuS proteins were produced in Escherichia coli and purified by immobilized metal affinity chromatography and ultrafiltration. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the abundance of the transcript of each gene. BoSus1 and BoSus3 may be duplicate or homeologous genes, the sequences of which show high identity. Similarly, BoSus2 shows high identity with BoSus4. Kinetic analysis showed that the two BoSuS isoforms of each type had similar michaelis constant (Km) values for sucrose, but different values for UDP. The four genes were expressed in various bamboo organs but were differentially regulated. The increase in the abundance of their mRNA paralleled the growth rate of the bamboo. The results suggest that, in bamboo, SuS is encoded by at least four genes, each with a specific role in providing substrates for the polysaccharide biosynthesis and/or energy production necessary to support the rapid growth of this species.

    View details for DOI 10.1111/j.1469-8137.2005.01638.x

    View details for Web of Science ID 000235731300008

    View details for PubMedID 16539603

  • Role for Arf3p in development of polarity, but not endocytosis, in Saccharomyces cerevisiae MOLECULAR BIOLOGY OF THE CELL Huang, C. F., Liu, Y. W., Tung, L., Lin, C. H., Lee, F. J. 2003; 14 (9): 3834-3847

    Abstract

    ADP-ribosylation factors (ARFs) are ubiquitous regulators of virtually every step of vesicular membrane traffic. Yeast Arf3p, which is most similar to mammalian ARF6, is not essential for cell viability and not required for endoplasmic reticulum-to-Golgi protein transport. Although mammalian ARF6 has been implicated in the regulation of early endocytic transport, we found that Arf3p was not required for fluid-phase, membrane internalization, or mating-type receptor-mediated endocytosis. Arf3p was partially localized to the cell periphery, but was not detected on endocytic structures. The nucleotide-binding, N-terminal region, and N-terminal myristate of Arf3p are important for its proper localization. C-Terminally green fluorescent protein-tagged Arf3, expressed from the endogenous promoter, exhibited a polarized localization to the cell periphery and buds, in a cell cycle-dependent manner. Arf3-GFP achieved its proper localization during polarity growth through an actin-independent pathway. Both haploid and homologous diploid arf3 mutants exhibit a random budding defect, and the overexpression of the GTP-bound form Arf3p(Q71L) or GDP-binding defective Arf3p(T31N) mutant interfered with budding-site selection. We conclude that the GTPase cycle of Arf3p is likely to be important for the function of Arf3p in polarizing growth of the emerging bud and/or an unidentified vesicular trafficking pathway.

    View details for DOI 10.1091/mbc.E03-01-0013

    View details for Web of Science ID 000185501600027

    View details for PubMedID 12972567

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