Chang-Hee Lee, and Taehoon ChunMol. Cells 2019; 42(1): 1-7 https://doi.org/10.14348/molcells.2018.0419
Abstract : Macrophage is an important innate immune cell that not only initiates inflammatory responses, but also functions in tissue repair and anti-inflammatory responses. Regulating macrophage activity is thus critical to maintain immune homeostasis. Tyro3, Axl, and Mer are integral membrane proteins that constitute TAM family of receptor tyrosine kinases (RTKs). Growing evidence indicates that TAM family receptors play an important role in anti-inflammatory responses through modulating the function of macrophages. First, macrophages can recognize apoptotic bodies through interaction between TAM family receptors expressed on macrophages and their ligands attached to apoptotic bodies. Without TAM signaling, macrophages cannot clear up apoptotic cells, leading to broad inflammation due to over-activation of immune cells. Second, TAM signaling can prevent chronic activation of macrophages by attenuating inflammatory pathways through particular pattern recognition receptors and cytokine receptors. Third, TAM signaling can induce autophagy which is an important mechanism to inhibit NLRP3 inflammasome activation in macrophages. Fourth, TAM signaling can inhibit polarization of M1 macrophages. In this review, we will focus on mechanisms involved in how TAM family of RTKs can modulate function of macrophage associated with anti-inflammatory responses described above. We will also discuss several human diseases related to TAM signaling and potential therapeutic strategies of targeting TAM signaling.
Sewoon Kim, and Sunjoo JeongMol. Cells 2019; 42(1): 8-16 https://doi.org/10.14348/molcells.2018.0436
Abstract : Mutations in the β-catenin gene (
Jae Min Park, Jae Eun Lee, Chan Mi Park, and Jung Hwa KimMol. Cells 2019; 42(1): 17-27 https://doi.org/10.14348/molcells.2018.0329
Abstract : Ubiquitin-specific protease 44 (USP44) has been implicated in tumor progression and metastasis across various tumors. However, the function of USP44 in prostate cancers and regulatory mechanism of histone-modifying enzymes by USP44 in tumors is not well-understood. Here, we found that enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, is regulated by USP44. We showed that EZH2 is a novel target of USP44 and that the protein stability of EZH2 is upregulated by USP44-mediated deubiquitination. In USP44 knockdown prostate cancer cells, the EZH2 protein level and its gene silencing activity were decreased. Furthermore, USP44 knockdown inhibited the tumorigenic characteristics and cancer stem cell-like behaviors of prostate cancer cells. Inhibition of tumorigenesis caused by USP44 knockdown was recovered by ectopic introduction of EZH2. Additionally, USP44 regulates the protein stability of oncogenic EZH2 mutants. Taken together, our results suggest that USP44 promotes the tumorigenesis of prostate cancer cells partly by stabilizing EZH2 and that USP44 is a viable therapeutic target for treating EZH2-dependent cancers.
Jisoo Park, Woochan Choi, Abdul Rouf Dar, Rebecca A. Butcher, and Kyuhyung KimMol. Cells 2019; 42(1): 28-35 https://doi.org/10.14348/molcells.2018.0380
Abstract : Animals need to be able to alter their developmental and behavioral programs in response to changing environmental conditions. This developmental and behavioral plasticity is mainly mediated by changes in gene expression. The knowledge of the mechanisms by which environmental signals are transduced and integrated to modulate changes in sensory gene expression is limited. Exposure to ascaroside pheromone has been reported to alter the expression of a subset of putative G protein-coupled chemosensory receptor genes in the ASI chemosensory neurons of
Weiye Dai, Taeyong Ryu, Hangun Kim, Yun Hye Jin, Young-Chang Cho, and Kwonseop KimMol. Cells 2019; 42(1): 36-44 https://doi.org/10.14348/molcells.2018.0273
Abstract : Alzheimer’s disease (AD) is the most frequent age-related human neurological disorder. The characteristics of AD include senile plaques, neurofibrillary tangles, and loss of synapses and neurons in the brain. β-Amyloid (Aβ) peptide is the predominant proteinaceous component of senile plaques. The amyloid hypothesis states that Aβ initiates the cascade of events that result in AD. Amyloid precursor protein (APP) processing plays an important role in Aβ production, which initiates synaptic and neuronal damage. δ-Catenin is known to be bound to presenilin-1 (PS-1), which is the main component of the γ-secretase complex that regulates APP cleavage. Because PS-1 interacts with both APP and δ-catenin, it is worth studying their interactive mechanism and/or effects on each other. Our immunoprecipitation data showed that there was no physical association between δ-catenin and APP. However, we observed that δ-catenin could reduce the binding between PS-1 and APP, thus decreasing the PS-1 mediated APP processing activity. Furthermore, δ-catenin reduced PS-1-mediated stabilization of APP. The results suggest that δ-catenin can influence the APP processing and its level by interacting with PS-1, which may eventually play a protective role in the degeneration of an Alzheimer’s disease patient.
Won-Mook Choi, Hyuk Soo Eun, Young-Sun Lee, Sun Jun Kim, Myung-Ho Kim, Jun-Hee Lee, Young-Ri Shim, Hee-Hoon Kim, Ye Eun Kim, Hyon-Seung Yi, and Won-Il JeongMol. Cells 2019; 42(1): 45-55 https://doi.org/10.14348/molcells.2018.0330
Abstract : The liver is involved in a wide range of activities in vertebrates and some other animals, including metabolism, protein synthesis, detoxification, and the immune system. Until now, various methods have been devised to study liver diseases; however, each method has its own limitations.
Ahjin Jung, Ji-Sook Yun, Shinae Kim, Sang Ryong Kim, Minsang Shin, Dong Hyung Cho, Kwang Shik Choi, and Jeong Ho ChangMol. Cells 2019; 42(1): 56-66 https://doi.org/10.14348/molcells.2018.0377
Abstract : Histidine triad nucleotide-binding protein (HINT) is a member of the histidine triad (HIT) superfamily, which has hydrolase activity owing to a histidine triad motif. The HIT superfamily can be divided to five classes with functions in galactose metabolism, DNA repair, and tumor suppression. HINTs are highly conserved from archaea to humans and function as tumor suppressors, translation regulators, and neuropathy inhibitors. Although the structures of HINT proteins from various species have been reported, limited structural information is available for fungal species. Here, to elucidate the structural features and functional diversity of HINTs, we determined the crystal structure of HINT from the pathogenic fungus
Hyehyeon Lee, Hyerin Jeong, Sun Young Lee, Soo Shin Kim, and Kyung Lib JangMol. Cells 2019; 42(1): 67-78 https://doi.org/10.14348/molcells.2018.0255
Abstract : Methylation of HBV cccDNA has been detected
Seokho Hong, Bokyung Son, Sangryeol Ryu, and Nam-Chul HaMol. Cells 2019; 42(1): 79-86 https://doi.org/10.14348/molcells.2018.0379
Abstract : Endolysins are bacteriophage-derived enzymes that hydrolyze the peptidoglycan of host bacteria. Endolysins are considered to be promising tools for the control of pathogenic bacteria. LysB4 is an endolysin produced by
Wonseok Shin, Seyoung Mun, Junse Kim, Wooseok Lee, Dong-Guk Park, Seungkyu Choi, Tae Yoon Lee, Seunghee Cha, and Kyudong HanMol. Cells 2019; 42(1): 87-95 https://doi.org/10.14348/molcells.2018.0351
Abstract : Long interspersed element-1 (LINE-1 or L1) is an autonomous retrotransposon, which is capable of inserting into a new region of genome. Previous studies have reported that these elements lead to genomic variations and altered functions by affecting gene expression and genetic networks. Mounting evidence strongly indicates that genetic diseases or various cancers can occur as a result of retrotransposition events that involve L1s. Therefore, the development of methodologies to study the structural variations and interpersonal insertion polymorphisms by L1 element-associated changes in an individual genome is invaluable. In this study, we applied a systematic approach to identify human-specific L1s (i.e., L1Hs) through the bioinformatics analysis of high-throughput next-generation sequencing data. We identified 525 candidates that could be inferred to carry non-reference L1Hs in a Korean individual genome (KPGP9). Among them, we randomly selected 40 candidates and validated that approximately 92.5% of non-reference L1Hs were inserted into a KPGP9 genome. In addition, unlike conventional methods, our relatively simple and expedited approach was highly reproducible in confirming the L1 insertions. Taken together, our findings strongly support that the identification of non-reference L1Hs by our novel target enrichment method demonstrates its future application to genomic variation studies on the risk of cancer and genetic disorders.