Takeshi Chujo, and Tetsuro HiroseMol. Cells 2017; 40(12): 889-896 https://doi.org/10.14348/molcells.2017.0263
Abstract : Nuclear bodies are subnuclear, spheroidal, and membraneless compartments that concentrate specific proteins and/or RNAs. They serve as sites of biogenesis, storage, and sequestration of specific RNAs, proteins, or ribonucleoprotein complexes. Recent studies reveal that a subset of nuclear bodies in various eukaryotic organisms is constructed using architectural long noncoding RNAs (arcRNAs). Here, we describe the unifying mechanistic principles of the construction and function of these bodies, especially focusing on liquid-liquid phase separation induced by architectural molecules that form multiple weakly adhesive interactions. We also discuss three possible advantages of using arcRNAs rather than architectural proteins to build the bodies: position-specificity, rapidity, and economy in sequestering nucleic acid-binding proteins. Moreover, we introduce two recently devised methods to discover novel arcRNA-constructed bodies; one that focuses on the RNase-sensitivity of these bodies, and another that focuses on “semi-extractability” of arcRNAs.
Taewook Nam, Jong Hyun Han, Sushil Devkota, and Han-Woong LeeMol. Cells 2017; 40(12): 897-905 https://doi.org/10.14348/molcells.2017.0226
Abstract : Cellular protein homeostasis is maintained by two major degradation pathways, namely the ubiquitin-proteasome system (UPS) and autophagy. Until recently, the UPS and autophagy were considered to be largely independent systems targeting proteins for degradation in the proteasome and lysosome, respectively. However, the identification of crucial roles of molecular players such as ubiquitin and p62 in both of these pathways as well as the observation that blocking the UPS affects autophagy flux and
Tae Woo Jung, Hyung Sub Park, Geum Hee Choi, Daehwan Kim, and Taeseung LeeMol. Cells 2017; 40(12): 906-915 https://doi.org/10.14348/molcells.2017.0097
Abstract : Impairment of wound healing is a common problem in individuals with diabetes. Adiponectin, an adipocyte-derived cytokine, has many beneficial effects on metabolic disorders such as diabetes, obesity, hypertension, and dyslipidemia. C1q/TNF-Related Protein 9 (CTRP9), the closest paralog of adiponectin, has been reported to have beneficial effects on wound healing. In the current study, we demonstrate that CTRP9 regulates growth, differentiation, and apoptosis of HaCaT human keratinocytes. We found that CTRP9 augmented expression of transforming growth factor beta 1 (TGFβ1) by transcription factor activator protein 1 (AP-1) binding activity and phosphorylation of p38 in a dose-dependent manner. Furthermore, siRNA-mediated suppression of TGFβ1 reversed the increase in p38 phosphorylation induced by CTRP9. siRNA-mediated suppression of TGFβ1 or p38 significantly abrogated the effects of CTRP9 on cell proliferation and differentiation while inducing apoptosis, implying that CTRP9 stimulates wound recovery through a TGFβ1-dependent pathway in keratinocytes. Furthermore, intravenous injection of CTRP9 via tail vein suppressed mRNA expression of Ki67 and involucrin whereas it augmented TGFβ1 mRNA expression and caspase 3 activity in skin of type 1 diabetes animal models. In conclusion, our results suggest that CTRP9 has suppressive effects on hyperkeratosis, providing a potentially effective therapeutic strategy for diabetic wounds.
Changlin Zhai, Qang Qian, Guanmin Tang, Bingjiang Han, Huilin Hu, Dong Yin, Haihua Pan, and Song ZhangMol. Cells 2017; 40(12): 916-924 https://doi.org/10.14348/molcells.2017.0164
Abstract : MicroRNAs are widely involved in the pathogenesis of cardiovascular diseases through regulating gene expression via translational inhibition or degradation of their target mRNAs. Recent studies have indicated a critical role of microRNA-206 in myocardial ischaemia-reperfusion (I/R) injury. However, the function of miR-206 in myocardial I/R injury is currently unclear. The present study was aimed to identify the specific role of miR-206 in myocardial I/R injury and explore the underlying molecular mechanism. Our results revealed that the expression level of miR-206 was significantly decreased both in rat I/R group and H9c2 cells subjected to hypoxia/reoxygenation (H/R) compared with the corresponding control. Overexpression of miR-206 observably decreased infarct size and inhibited the cardiomyocyte apoptosis induced by I/R injury. Furthermore, bioinformatics analysis, luciferase activity and western blot assay proved that Gadd45β (growth arrest DNA damage-inducible gene 45β) was a direct target gene of miR-206. In addition, the expression of pro-apoptotic-related genes, such as p53, Bax and cleaved caspase3, was decreased in association with the down-regulation of Gadd45β. In summary, this study demonstrates that miR-206 could protect against myocardial I/R injury by targeting Gadd45β.
Gwang Su Kim, Inyoung Lee, Ji Hun Kim, and Deog Su HwangMol. Cells 2017; 40(12): 925-934 https://doi.org/10.14348/molcells.2017.0191
Abstract : The Cdc6 protein is essential for the initiation of chromosomal replication and functions as a licensing factor to maintain chromosome integrity. During the S and G2 phases of the cell cycle, Cdc6 has been found to inhibit the recruitment of pericentriolar material (PCM) proteins to the centrosome and to suppress centrosome over-duplication. In this report, we analyzed the correlation between these two functions of Cdc6 at the centrosome. Cdc6 depletion increased the population of cells showing centrosome over-duplication and premature centrosome separation; Cdc6 expression reversed these changes. Deletion and fusion experiments revealed that the 18 amino acid residues (197?214) of Cdc6, which were fused to the Cdc6-centrosomal localization signal, suppressed centrosome over-duplication and premature centrosome separation. Cdc6 mutant proteins that showed defective ATP binding or hydrolysis did not exhibit a significant difference in suppressing centrosome over-duplication, compared to the wild type protein. In contrast to the Cdc6-mediated inhibition of PCM protein recruitment to the centrosome, the independence of Cdc6 on its ATPase activity for suppressing centrosome over-duplication, along with the difference between the Cdc6 protein regions participating in the two functions, suggested that Cdc6 controls centrosome duplication in a manner independent of its recruitment of PCM proteins to the centrosome.
Gyu-Lee Kim, Truc Thanh Luong, Sang-Sang Park, Seungyeop Lee, Jung Ah Ha, Cuong Thach Nguyen, Ji Hye Ahn, Ki-Tae Park, Man-Jeong Paik, Suhkneung-Pyo, David E. Briles, and Dong-Kwon RheeMol. Cells 2017; 40(12): 935-944 https://doi.org/10.14348/molcells.2017.0201
Abstract : More than 50% of sepsis cases are associated with pneumonia. Sepsis is caused by infiltration of bacteria into the blood via inflammation, which is triggered by the release of cell wall components following lysis. However, the regulatory mechanism of lysis during infection is not well defined. Mice were infected with
Ajeet Kumar, Tae-Lin Huh, Joonho Choe, and Myungchull RheeMol. Cells 2017; 40(12): 945-953 https://doi.org/10.14348/molcells.2017.0216
Abstract : We report the biological functions of a zebrafish homologue of RING-finger protein 152 (
Sang Eun Ryu, Tammy Shim, Ju-Yeon Yi, So Yeun Kim, Sun Hwa Park, Sung Won Kim, Gabriele V. Ronnett, and Cheil MoonMol. Cells 2017; 40(12): 954-965 https://doi.org/10.14348/molcells.2017.0223
Abstract : Mammalian genomes are well established, and highly conserved regions within odorant receptors that are unique from other G-protein coupled receptors have been identified. Numerous functional studies have focused on specific conserved amino acids motifs; however, not all conserved motifs have been sufficiently characterized. Here, we identified a highly conserved 18 amino acid sequence motif within transmembrane domain seven (CAS-TM7) which was identified by aligning odorant receptor sequences. Next, we investigated the expression pattern and distribution of this conserved amino acid motif among a broad range of odorant receptors. To examine the localization of odorant receptor proteins, we used a sequence-specific peptide antibody against CAS-TM7 which is specific to odorant receptors across species. The specificity of this peptide antibody in recognizing odorant receptors has been confirmed in a heterologous
Laila Khaleda, Hee Jin Park, Dae-Jin Yun, Jong-Rok Jeon, Min Gab Kim, Joon-Yung Cha, and Woe-Yeon KimMol. Cells 2017; 40(12): 966-975 https://doi.org/10.14348/molcells.2017.0229
Abstract : Excessive salt disrupts intracellular ion homeostasis and inhibits plant growth, which poses a serious threat to global food security. Plants have adapted various strategies to survive in unfavorable saline soil conditions. Here, we show that humic acid (HA) is a good soil amendment that can be used to help overcome salinity stress because it markedly reduces the adverse effects of salinity on
Sunggyu Yoon, Bumsik Cho, Mingyu Shin, Ferdinand Koranteng, Nuri Cha, and Jiwon ShimMol. Cells 2017; 40(12): 976-985 https://doi.org/10.14348/molcells.2017.0287
Abstract : Iron is an essential divalent ion for aerobic life. Life has evolved to maintain iron homeostasis for normal cellular and physiological functions and therefore imbalances in iron levels exert a wide range of consequences. Responses to iron dysregulation in blood development, however, remain elusive. Here, we found that iron homeostasis is critical for differentiation of