Hye-Ra Lee, Un Yung Choi, Sung-Woo Hwang, Stephanie Kim, and Jae U. JungMol. Cells 2016; 39(11): 777-782 https://doi.org/10.14348/molcells.2016.0232
Abstract : The innate immune system has evolved to detect and destroy invading pathogens before they can establish systemic infection. To successfully eradicate pathogens, including viruses, host innate immunity is activated through diverse pattern recognition receptors (PRRs) which detect conserved viral signatures and trigger the production of type I interferon (IFN) and pro-inflammatory cytokines to mediate viral clearance. Viral persistence requires that viruses co-opt cellular pathways and activities for their benefit. In particular, due to the potent antiviral activities of IFN and cytokines, viruses have developed various strategies to meticulously modulate intracellular innate immune sensing mechanisms to facilitate efficient viral replication and persistence. In this review, we highlight recent advances in the study of viral immune evasion strategies with a specific focus on how Kaposi’s sarcoma-associated herpesvirus (KSHV) effectively targets host PRR signaling pathways.
Min Jee Kwon, Sunhong Kim, Myeong Hoon Han, and Sung Bae LeeMol. Cells 2016; 39(11): 783-789 https://doi.org/10.14348/molcells.2016.0233
Abstract : Afflicted neurons in various neurodegenerative diseases generally display diverse and complex pathological features before catastrophic occurrence of massive neuronal loss at the late stages of the diseases. This complex nature of neuronal pathophysiology inevitably implicates systemwide changes in basic cellular activities such as transcriptional controls and signal cascades, and so on, as a cause. Recently, as one of these systemwide cellular changes associated with neurodegenerative diseases, epigenetic changes caused by protein toxicity have begun to be highlighted. Notably, recent advances in related techniques including next-generation sequencing (NGS) and mass spectrometry enable us to monitor changes in the post-translational modifications (PTMs) of histone proteins and to link these changes in histone PTMs to the specific transcriptional changes. Indeed, epigenetic alterations and consequent changes in neuronal transcriptome are now begun to be extensively studied in neurodegenerative diseases including Alzheimer’s disease (AD). In this review, we will discuss details of our current understandings on epigenetic changes associated with two representative neurodegenerative diseases [AD and polyglutamine (polyQ) diseases] and further discuss possible future development of pharmaceutical treatment of the diseases through modulating these epigenetic changes.
Ji-Hye Kim, Gee-Hye Kim, Jae-Won Kim, Hee Jang Pyeon, Jae Cheoun Lee, Gene Lee, and Hyun NamMol. Cells 2016; 39(11): 790-796 https://doi.org/10.14348/molcells.2016.0131
Abstract : Dental pulp is a highly vascularized tissue requiring adequate blood supply for successful regeneration. In this study, we investigated the functional role of stem cells from human exfoliated deciduous teeth (SHEDs) as a perivascular source for
Zhang Guo Hua, Lu Jian Xiong, Chen Yan, Dai Hong Wei, ZhaXi YingPai, Zhao Yong Qing, Qiao Zi Lin, Feng Ruo Fei, Wang Ya Ling, and Ma Zhong RenMol. Cells 2016; 39(11): 797-806 https://doi.org/10.14348/molcells.2016.0144
Abstract : Lipogenesis is under the concerted action of ChREBP, SREBP-1c and other transcription factors in response to glucose and insulin. The isolated porcine preadipocytes were differentiated into mature adipocytes to investigate the roles and interrelation of these transcription factors in the context of glucose- and insulin-induced lipogenesis in pigs. In ChREBP-silenced adipocytes, glucose-induced lipogenesis decreased by ~70%, however insulin-induced lipogenesis was unaffected. Moreover, insulin had no effect on ChREBP expression of unperturbed adipocytes irrespective of glucose concentration, suggesting ChREBP mediate glucose-induced lipogenesis. Insulin stimulated SREBP-1c expression and when SREBP-1c activation was blocked, and the insulin-induced lipogenesis decreased by ~55%, suggesting SREBP-1c is a key transcription factor mediating insulin-induced lipogenesis. LXRα activation promoted lipogenesis and lipogenic genes expression. In ChREBP-silenced or SREBP-1c activation blocked adipocytes, LXRα activation facilitated lipogenesis and SREBP-1c expression, but had no effect on ChREBP expression. Therefore, LXRα might mediate lipogenesis via SREBP-1c rather than ChREBP. When ChREBP expression was silenced and SREBP-1c activation blocked simultaneously, glucose and insulin were still able to stimulated lipogenesis and lipogenic genes expression, and LXRα activation enhanced these effects, suggesting LXRα mediated directly glucose- and insulin-induced lipogenesis. In summary, glucose and insulin stimulated lipogenesis through both dissimilar and identical regulation pathway in porcine adipocytes.
Pooja Dua, Shuo Ren, Sang Wook Lee, Joon-Ki Kim, Hye-su Shin, OK-Chan Jeong, Soyoun Kim, and Dong-Ki LeeMol. Cells 2016; 39(11): 807-813 https://doi.org/10.14348/molcells.2016.0167
Hwajung Choi, Kyungjin Min, Bunzo Mikami, Hye-Jin Yoon, and Hyung Ho LeeMol. Cells 2016; 39(11): 814-820 https://doi.org/10.14348/molcells.2016.0202
Abstract : FtsZ, a tubulin homologue, is an essential protein of the Z-ring assembly in bacterial cell division. It consists of two domains, the N-terminal and C-terminal core domains, and has a conserved C-terminal tail region. Lateral interactions between FtsZ protofilaments and several Z-ring associated proteins (Zaps) are necessary for modulating Z-ring formation. ZapD, one of the positive regulators of Z-ring assembly, directly binds to the C-terminal tail of FtsZ and promotes stable Z-ring formation during cytokinesis. To gain structural and functional insights into how ZapD interacts with the C-terminal tail of FtsZ, we solved two crystal structures of ZapD proteins from
Minkyung Shin, Eun Hee Yi, Byung-Hak Kim, Jae-Cheon Shin, Jung Youl Park, Chung-Hyun Cho, Jong-Wan Park, Kang-Yell Choi, and Sang-Kyu YeMol. Cells 2016; 39(11): 821-826 https://doi.org/10.14348/molcells.2016.0212
Abstract : The β-catenin functions as an adhesion molecule and a component of the Wnt signaling pathway. In the absence of the Wnt ligand, β-catenin is constantly phosphorylated, which designates it for degradation by the APC complex. This process is one of the key regulatory mechanisms of β-catenin. The level of β-catenin is also controlled by the E3 ubiquitin protein ligase SIAH-1 via a phosphorylation-independent degradation pathway. Similar to β-catenin, STAT3 is responsible for various cellular processes, such as survival, proliferation, and differentiation. However, little is known about how these molecules work together to regulate diverse cellular processes. In this study, we investigated the regulatory relationship between STAT3 and β-catenin in HEK293T cells. To our knowledge, this is the first study to report that β-catenin-TCF-4 transcriptional activity was suppressed by phosphorylated STAT3; furthermore, STAT3 inactivation abolished this effect and elevated activated β-catenin levels. STAT3 also showed a strong interaction with SIAH-1, a regulator of active β-catenin via degradation, which stabilized SIAH-1 and increased its interaction with β-catenin. These results suggest that activated STAT3 regulates active β-catenin protein levels via stabilization of SIAH-1 and the subsequent ubiquitin-dependent proteasomal degradation of β-catenin in HEK293T cells.
Weixun Li, Tae-Woo Choi, Joohong Ahnn, and Sun-Kyung LeeMol. Cells 2016; 39(11): 827-833 https://doi.org/10.14348/molcells.2016.0222
Abstract : Regulator of calcineurin 1 (RCAN1) binds to calcineurin through the PxIxIT motif, which is evolutionarily conserved. SP repeat phosphorylation in RCAN1 is required for its complete function. The specific interaction between RCAN1 and calcineurin is critical for calcium/calmodulin-dependent regulation of calcineurin serine/threonine phosphatase activity. In this study, we investigated two available deletion
Miseol Son, Ichiro Kawasaki, Bong-Kyeong Oh, and Yhong-Hee ShimMol. Cells 2016; 39(11): 834-840 https://doi.org/10.14348/molcells.2016.0238