Ukhyun Jo, and Hyungjin KimMol. Cells 2015; 38(8): 669-676 https://doi.org/10.14348/molcells.2015.0175
Abstract : Genome instability, primarily caused by faulty DNA repair mechanisms, drives tumorigenesis. Therapeutic interventions that exploit deregulated DNA repair in cancer have made considerable progress by targeting tumor-specific alterations of DNA repair factors, which either induces synthetic lethality or augments the efficacy of conventional chemotherapy and radiotherapy. The study of Fanconi anemia (FA), a rare inherited blood disorder and cancer predisposition syndrome, has been instrumental in understanding the extent to which DNA repair defects contribute to tumorigenesis. The FA pathway functions to resolve blocked replication forks in response to DNA interstrand cross-links (ICLs), and accumulating knowledge of its activation by the ubiquitin-mediated signaling pathway has provided promising therapeutic opportunities for cancer treatment. Here, we discuss recent advances in our understanding of FA pathway regulation and its potential application for designing tailored therapeutics that take advantage of deregulated DNA ICL repair in cancer.
Hyeonkyeong Kim, Donghyun Kang, Yongsik Cho, and Jin-Hong KimMol. Cells 2015; 38(8): 677-684 https://doi.org/10.14348/molcells.2015.0200
Abstract : Osteoarthritis (OA) is one of the most prevalent forms of joint disorder, associated with a tremendous socioeconomic burden worldwide. Various non-genetic and lifestyle-related factors such as aging and obesity have been recognized as major risk factors for OA, underscoring the potential role for epigenetic regulation in the pathogenesis of the disease. OA-associated epigenetic aberrations have been noted at the level of DNA methylation and histone modification in chondrocytes. These epigenetic regulations are implicated in driving an imbalance between the expression of catabolic and anabolic factors, leading eventually to osteoarthritic cartilage destruction. Cellular senescence and metabolic abnormalities driven by OA-associated risk factors appear to accompany epigenetic drifts in chondrocytes. Notably, molecular events associated with metabolic disorders influence epigenetic regulation in chondrocytes, supporting the notion that OA is a metabolic disease. Here, we review accumulating evidence supporting a role for epigenetics in the regulation of cartilage homeostasis and OA pathogenesis.
Won Kyong Cho, Tae Kyung Hyun, Dhinesh Kumar, Yeonggil Rim, Xiong Yan Chen, Yeonhwa Jo, Suwha Kim, Keun Woo Lee, Zee-Yong Park, William J. Lucas, and Jae-Yean KimMol. Cells 2015; 38(8): 685-696 https://doi.org/10.14348/molcells.2015.0033
Abstract : Rice is a model plant widely used for basic and applied research programs. Plant cell wall proteins play key roles in a broad range of biological processes. However, presently, knowledge on the rice cell wall proteome is rudimentary in nature. In the present study, the tightly-bound cell wall proteome of rice callus cultured cells using sequential extraction protocols was developed using mass spectrometry and bioinformatics methods, leading to the identification of 1568 candidate proteins. Based on bioinformatics analyses, 389 classical rice cell wall proteins, possessing a signal peptide, and 334 putative non-classical cell wall proteins, lacking a signal peptide, were identified. By combining previously established rice cell wall protein databases with current data for the classical rice cell wall proteins, a comprehensive rice cell wall proteome, comprised of 496 proteins, was constructed. A comparative analysis of the rice and
Jihye Lee, Guillaume Adelmant, Jarrod A. Marto, and Dong-Hyun LeeMol. Cells 2015; 38(8): 697-704 https://doi.org/10.14348/molcells.2015.0066
Abstract : Deleted in breast cancer-1 (DBC1) contributes to the regulation of cell survival and apoptosis. Recent studies demonstrated that DBC is phosphorylated at Thr454 by ATM/ATR kinases in response to DNA damage, which is a critical event for p53 activation and apoptosis. However, how DBC1 phosphorylation is regulated has not been studied. Here we show that protein phosphatase 4 (PP4) dephosphorylates DBC1, regulating its role in DNA damage response. PP4R2, a regulatory subunit of PP4, mediates the interaction between DBC1 and PP4C, a catalytic subunit. PP4C efficiently dephosphorylates pThr454 on DBC1
Youngmi Kim, Hyuna Kim, and Dooil JeoungMol. Cells 2015; 38(8): 705-714 https://doi.org/10.14348/molcells.2015.0086
Abstract : We investigated the role of HDAC3 in anti-cancer drug-resistance. The expression of HDAC3 was decreased in cancer cell lines resistant to anti-cancer drugs such as celastrol and taxol. HDAC3 conferred sensitivity to these anti-cancer drugs. HDAC3 activity was necessary for conferring sensitivity to these anti-cancer drugs. The down-regulation of HDAC3 increased the expression of MDR1 and conferred resistance to anti-cancer drugs. The expression of tubulin β3 was increased in drug-resistant cancer cell lines. ChIP assays showed the binding of HDAC3 to the promoter sequences of tubulin β3 and HDAC6. HDAC6 showed an interaction with tubulin β3. HDAC3 had a negative regulatory role in the expression of tubulin β3 and HDAC6. The down-regulation of HDAC6 decreased the expression of MDR1 and tubulin β3, but did not affect HDAC3 expression. The down-regulation of HDAC6 conferred sensitivity to taxol. The down-regulation of tubulin β3 did not affect the expression of HDAC6 or MDR1. The down-regulation of tubulin β3 conferred sensitivity to anti-cancer drugs. Our results showed that tubulin β3 serves as a downstream target of HDAC3 and mediates resistance to microtubule-targeting drugs. Thus, the HDAC3-HDAC6-Tubulin β axis can be employed for the development of anti-cancer drugs.
Si-Hyeon Um, Jin-Sik Kim, Saemee Song, Nam Ah Kim, Seong Hoon Jeong, and Nam-Chul HaMol. Cells 2015; 38(8): 715-722 https://doi.org/10.14348/molcells.2015.0099
Abstract : In Gram-negative bacteria in the periplasmic space, the dimeric thioredoxin-fold protein DsbC isomerizes and reduces incorrect disulfide bonds of unfolded proteins, while the monomeric thioredoxin-fold protein DsbA introduces disulfide bonds in folding proteins. In the Gram-negative bacteria
Boksik Cha, Yaerin Park, Byul Nim Hwang, So-young Kim, and Eek-hoon JhoMol. Cells 2015; 38(8): 723-728 https://doi.org/10.14348/molcells.2015.0113
Abstract : Smurf2, a member of the HECT domain E3 ligase family, is well known for its role as a negative regulator of TGF-β signaling by targeting Smads and TGF-β receptor. However, the regulatory mechanism of Smurf2 has not been elucidated. Arginine methylation is a type of post-translational modification that produces monomethylated or dimethylated arginine residues. In this report, we demonstrated methylation of Smurf2 by PRMT1.
Injeong Cho, Gyu Jin Hwang, and Jeong Hoon ChoMol. Cells 2015; 38(8): 729-733 https://doi.org/10.14348/molcells.2015.0124
Min-yeong Lee, Seokheon Hong, Nahmhee Kim, Ki Soon Shin, and Shin Jung KangMol. Cells 2015; 38(8): 734-740 https://doi.org/10.14348/molcells.2015.0131
Abstract : Recent studies report that a history of antidepressant use is strongly correlated with the occurrence of Parkinson’s disease (PD). However, it remains unclear whether antidepressant use can be a causative factor for PD. In the present study, we examined whether tricyclic antidepressants amitriptyline and desipramine can induce dopaminergic cell damage, both
Suho Lee, Hyunji Moon, Gayoung Kim, Jeong Hoon Cho, Dae-Hee Lee, Michael B. Ye, and Daeho ParkMol. Cells 2015; 38(8): 741-741 https://doi.org/10.14348/molcells.2015.1083