Biomedical subjects

Jaesang Kim

Publications and source records attributed to Jaesang Kim.

9 recordsLinked to original sources

PubMed2006

ECgene: an alternative splicing database update.

ECgene (http://genome.ewha.ac.kr/ECgene) was developed to provide functional annotation for alternatively spliced genes. The applications encompass the genome-based transcript modeling for alternative splicing (AS), domain analysis with Gene Ontology (GO) annotation and expression analysis based on the EST and SAGE data. We have expanded the ECgene's AS modeling and EST clustering to nine organisms for which sufficient EST data are available in the GenBank. As for the human genome, we have also introduced several new applications to analyze differential expression. ECprofiler is an ontology-based candidate gene search system that allows users to select an arbitrary combination of gene expression pattern and GO functional categories. DEGEST is a database of differentially expressed genes and isoforms based on the EST information. Importantly, gene expression is analyzed at three distinctive levels-gene, isoform and exon levels. The user interfaces for functional and expression analyses have been substantially improved. ASviewer is a dedicated java application that visualizes the transcript structure and functional features of alternatively spliced variants. The SAGE part of the expression module provides many additional features including SNP, differential expression and alternative tag positions.

Alternative Splicing↗

PubMed2006

An essential complementary role of NF-kappaB pathway to microbicidal oxidants in Drosophila gut immunity.

In the Drosophila gut, reactive oxygen species (ROS)-dependent immunity is critical to host survival. This is in contrast to the NF-kappaB pathway whose physiological function in the microbe-laden epithelia has yet to be convincingly demonstrated despite playing a critical role during systemic infections. We used a novel in vivo approach to reveal the physiological role of gut NF-kappaB/antimicrobial peptide (AMP) system, which has been 'masked' in the presence of the dominant intestinal ROS-dependent immunity. When fed with ROS-resistant microbes, NF-kappaB pathway mutant flies, but not wild-type flies, become highly susceptible to gut infection. This high lethality can be significantly reduced by either re-introducing Relish expression to Relish mutants or by constitutively expressing a single AMP to the NF-kappaB pathway mutants in the intestine. These results imply that the local 'NF-kappaB/AMP' system acts as an essential 'fail-safe' system, complementary to the ROS-dependent gut immunity, during gut infection with ROS-resistant pathogens. This system provides the Drosophila gut immunity the versatility necessary to manage sporadic invasion of virulent pathogens that somehow counteract or evade the ROS-dependent immunity.

Animals↗

PubMed2006

Basic helix-loop-helix gene Hes6 delineates the sensory hair cell lineage in the inner ear.

The basic helix-loop-helix (bHLH) gene Hes6 is known to promote neural differentiation in vitro. Here, we report the expression and functional studies of Hes6 in the inner ear. The expression of Hes6 appears to be parallel to that of Math1 (also known as Atoh1), a bHLH gene necessary and sufficient for hair cell differentiation. Hes6 is expressed initially in the presumptive hair cell precursors in the cochlea. Subsequently, the expression of Hes6 is restricted to morphologically differentiated hair cells. Similarly, the expression of Hes6 in the vestibule is in the hair cell lineage. Hes6 is dispensable for hair cell differentiation, and its expression in inner ear hair cells is abolished in the Math1-null animals. Furthermore, the introduction of Hes6 into the cochlea in vitro is not sufficient to promote sensory or neuronal differentiation. Therefore, Hes6 is downstream of Math1 and its expression in the inner ear delineates the sensory lineage. However, the role of Hes6 in the inner ear remains elusive.

Animals↗

PubMed2006

Down-regulation of Sox10 with specific small interfering RNA promotes transdifferentiation of Schwannoma cells into myofibroblasts.

Neural crest-derived cells are noted for the long lasting plasticity during lineage commitment process and the potential for transdifferentiation into other neural crest derivatives. Schwann cells in particular have been reported to transdifferentiate into melanocytes and myofibroblasts. Detailed studies of transdifferentiation at the molecular level have been hampered by difficulty in isolating sufficient quantity of primary cells or cellular materials. Here, we describe a robust in vitro system in which Schwannoma cells undergo an apparent transdifferentiation into myofibroblasts. Importantly, we induce the transdifferentiation by down-regulating a single transcription factor, Sox10, thereby identifying a key molecular event in this process. Myofibroblasts thus generated showed carbachol-stimulated contraction and calcium transients and express several established myofibroblast-specific genes. These results suggest that generating desired cell types based on "knock-down" of critical genes may be a viable strategy.

Actins↗

PubMed2005

The conserved WRPW motif of Hes6 mediates proteasomal degradation.

Hes6 belongs to a subfamily of basic helix-loop-helix transcription factors that includes Drosophila Hairy and Enhancer of split genes. Like other members of the family, Hes6 features the WRPW motif which is consisted just of four amino acids at its C-terminus. Here, we show that WRPW motif deletion mutant protein is substantially stabilized in comparison to the full length protein and that the enhanced stability is due to its resistance to proteasomal degradation. The WRPW motif also appears to be sufficient for acceleration of proteolysis as its fusion to two heterologous proteins, the green fluorescent protein (GFP) of Aequoria victoria and Gal4 DNA binding domain of Saccharomyces cerevisiae, significantly destabilized the proteins. These findings demonstrate a novel function of this conserved motif as a degradation signal and raise the possibility of utilizing it for controlling the level of ectopically expressed gene products.

Amino Acid Motifs↗

PubMed2004

Cutting edge: direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappa B.

LPS, the primary constituent of the outer membrane of Gram-negative bacteria, is recognized by TLR4. Binding of TLR4 to LPS triggers various cell signaling pathways including NF-kappaB activation and reactive oxygen species (ROS) production. In this study, we present the data that LPS-induced ROS generation and NF-kappaB activation are mediated by a direct interaction of TLR4 with (NAD(P)H oxidase 4 (Nox) 4), a protein related to gp91phox (Nox2) of phagocytic cells, in HEK293T cells. Yeast two hybrid and GST pull-down assays indicated that the COOH-terminal region of Nox4 interacted with the cytoplasmic tail of TLR4. Knockdown of Nox4 by transfection of small interference RNA specific to the Nox4 isozyme in HEK293T cells expressing TLR4 along with MD2 and CD14 resulted in inhibition of LPS-induced ROS generation and NF-kappaB activation. Taken together, these results indicate that direct interaction of TLR4 with Nox4 is involved in LPS-mediated ROS generation and NF-kappaB activation.

Cell Line↗

PubMed2004

PIAS3 suppresses NF-kappaB-mediated transcription by interacting with the p65/RelA subunit.

Nuclear factor-kappaB (NF-kappaB) is a transcription factor critical for key cellular processes, including immune response, apoptosis, and cell cycle progression. A yeast two-hybrid screening, using the Rel homology domain (RHD) of the p65 subunit (RelA) of NF-kappaB as bait, led to the isolation of PIAS3, previously identified as a specific inhibitor of STAT3. We show that PIAS3 can directly associate with p65 using an in vitro pull-down and in vivo coimmunoprecipitation assays. When overexpressed, PIAS3 inhibits NF-kappaB-dependent transcription induced by treatment with tumor necrosis factor alpha (TNF-alpha) or interleukin-1beta or by overexpression of TNF family receptors such as RANK, TNFR1, and CD30 or signal transducers of TNF receptor-associated factors (TRAFs), including TRAF2, TRAF5, and TRAF6. Downregulation of PIAS3 by RNA interference reverses its effect on TNF-alpha-mediated NF-kappaB activation. We found that an N-terminal region of PIAS3 is necessary for both the interaction with p65 and the transcriptional suppression activity. In addition, we found that an LXXLL coregulator signature motif located within the N-terminal region of PIAS3 is the minimal requirement for the interaction with p65. Furthermore, we demonstrate that PIAS3 interferes with p65 binding to the CBP coactivator, thereby resulting in a decreased NF-kappaB-dependent transcription. Taken together, these data suggest that PIAS3 may function in vivo as a modulator in suppressing the transcriptional activity of p65.

Amino Acid Motifs↗

PubMed2003

SOX10 maintains multipotency and inhibits neuronal differentiation of neural crest stem cells.

The mechanisms that establish and maintain the multipotency of stem cells are poorly understood. In neural crest stem cells (NCSCs), the HMG-box factor SOX10 preserves not only glial, but surprisingly, also neuronal potential from extinction by lineage commitment signals. The latter function is reflected in the requirement of SOX10 in vivo for induction of MASH1 and PHOX2B, two neurogenic transcription factors. Simultaneously, SOX10 inhibits or delays overt neuronal differentiation, both in vitro and in vivo. However, this activity requires a higher Sox10 gene dosage than does the maintenance of neurogenic potential. The opponent functions of SOX10 to maintain neural lineage potentials, while simultaneously serving to inhibit or delay neuronal differentiation, suggest that it functions in stem or progenitor cell maintenance, in addition to its established role in peripheral gliogenesis.

Animals↗

PubMed2002

Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity.

The neural bHLH genes Mash1 and Ngn2 are expressed in complementary populations of neural progenitors in the central and peripheral nervous systems. Here, we have systematically compared the activities of the two genes during neural development by generating replacement mutations in mice in which the coding sequences of Mash1 and Ngn2 were swapped. Using this approach, we demonstrate that Mash1 has the capacity to respecify the identity of neuronal populations normally derived from Ngn2-expressing progenitors in the dorsal telencephalon and ventral spinal cord. In contrast, misexpression of Ngn2 in Mash1-expressing progenitors does not result in any overt change in neuronal phenotype. Taken together, these results demonstrate that Mash1 and Ngn2 have divergent functions in specification of neuronal subtype identity, with Mash1 having the characteristics of an instructive determinant whereas Ngn2 functions as a permissive factor that must act in combination with other factors to specify neuronal phenotypes. Moreover, the ectopic expression of Ngn2 can rescue the neurogenesis defects of Mash1 null mutants in the ventral telencephalon and sympathetic ganglia but not in the ventral spinal cord and the locus coeruleus, indicating that Mash1 contribution to the specification of neuronal fates varies greatly in different lineages, presumably depending on the presence of other determinants of neuronal identity.

Animals↗