Molecules and Cells Editor’s Choice 2023 논문 소개
Molecules and Cells는 1990년 창간된 이후, 1995년 국내 생명과학분야 최초로 SCI에 등재된 30년이 넘은 전통성을 갖고 있는 국제학술지로서 1990년 창간호부터 현재까지 30개국 이상의 국가에서 좋은 연구 논문이 투고되어 국제적으로 공고한 입지를 가지고 있다. 본 Molecules and Cells Editor’s Choice에서는 2023년에 본지에 게재된 4편의 우수한 research article을 선정하여 성과를 홍보하고자 합니다.
1. Mol. Cells 2023; 46(6), 360-373
Yuan Shao, Wanli Ren, Hao Dai, Fangli Yang, Xiang Li, Shaoqiang Zhang, Junsong Liu, Xiaobao Yao, Qian Zhao, Xin Sun, Zhiwei Zheng, and Chongwen Xu
Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid carcinoma. Despite a good prognosis, approximately a quarter of PTC patients are likely to relapse. Previous reports suggest an association between S-phase kinase-associated protein 2 (SKP2) and the prognosis of thyroid cancer. SKP1 is related to apoptosis of PTC cells; however, its role in PTC remains largely elusive. This study aimed to understand the expression and molecular mechanism of SKP2 in PTC. SKP2 expression was upregulated in PTC tissues and closely associated with clinical diagnosis. In vitro and in vivo knockdown of SKP2 expression in PTC cells suppressed cell growth and proliferation and induced apoptosis. SKP2 depletion promoted cell autophagy under glucose deprivation. SKP2 interacted with PH domain leucine-rich repeat protein phosphatase-1 (PHLPP1), triggering its degradation by ubiquitination. Furthermore, SKP2 activates the AKT-related pathways via PHLPP1, which leads to the cytoplasmic translocation of SKP2, indicating a reciprocal regulation between SKP2 and AKT. In conclusion, the upregulation of SKP2 leads to PTC proliferation and survival, and the regulatory network among SKP2, PHLPP1, and AKT provides novel insight into the molecular basis of SKP2 in tumor progression.
Keywords: AKT, papillary thyroid carcinoma, PH domain leucine-rich repeat protein phosphatase-1, S-phase kinase-associated protein 2
이 논문은 S-phase kinase-associated protein 2 (SKP2) 단백질이 PH domain leucine-rich repeat protein phosphatase-1 (PHLPP1)의 유비퀴틴화와 이에 따른 분해를 통해 AKT 경로를 활성화시키고 갑상선 암세포의 생존을 촉진하는 암생물학의 새로운 메커니즘을 규명한 논문으로서, 갑상선 암의 진행과 생존에 중요한 역할을 하는 SKP2의 작동을 제어하는 새로운 치료 전략을 제시합니다.
2. Mol. Cells 2023; 46(4), 245-255
Jeong-Yeon Seo, Tae-Hyeon Kim, Kyeong-Rok Kang, HyangI Lim, Moon-Chang Choi, Do Kyung Kim, Hong Sung Chun, Heung-Joong Kim, Sun-Kyoung Yu, Jae-Sung Kim
This study aimed to exploring the pathophysiological mechanism of 7α,25-dihydroxycholesterol (7α,25-DHC) in osteoarthritis (OA) pathogenesis. 7α,25-DHC accelerated the proteoglycan loss in ex vivo organ-cultured articular cartilage explant. It was mediated by the decreasing extracellular matrix major components, including aggrecan and type II collagen, and the increasing expression and activation of degenerative enzymes, including matrix metalloproteinase (MMP)-3 and -13, in chondrocytes cultured with 7α,25-DHC. Furthermore, 7α,25-DHC promoted caspase dependent chondrocytes death via extrinsic and intrinsic pathways of apoptosis. Moreover, 7α,25-DHC upregulated the expression of inflammatory factors, including inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2, via the production of reactive oxygen species via increase of oxidative stress in chondrocytes. In addition, 7α,25-DHC upregulated the expression of autophagy biomarker, including beclin-1 and microtubule-associated protein 1A/1B-light chain 3 via the modulation of p53-Akt-mTOR axis in chondrocytes. The expression of CYP7B1, caspase-3, and beclin-1 was elevated in the degenerative articular cartilage of mouse knee joint with OA. Taken together, our findings suggest that 7α,25-DHC is a pathophysiological risk factor of OA pathogenesis that is mediated a chondrocytes death via oxiapoptophagy, which is a mixed mode of apoptosis, oxidative stress, and autophagy.
Keywords: 25-dihydroxycholesterol; 7α; chondrocytes; osteoarthritis.
본 논문은 7α,25-디하이드록시콜레스테롤(7α,25-DHC)이 산화 스트레스, 자가포식 및 세포 자멸에 영향을 미쳐 연골퇴행을 촉진하는 메커니즘을 밝힌 논문으로서, 7α,25-DHC가 골관절염 발병의 병리학적 위험 인자임을 시사하며, 새로운 치료 표적이 될 수 있음을 제시합니다.
3. Mol. Cells 2023; 46(8), 486-495
Lipofuscin Granule Accumulation Requires Autophagy Activation
Seon Beom Song, Woosung Shim, Eun Seong Hwang
Lipofuscins are oxidized lipid and protein complexes that accumulate during cellular senescence and tissue aging, regarded as markers for cellular oxidative damage, tissue aging, and certain aging-associated diseases. Therefore, understanding their cellular biological properties is crucial for effective treatment development. Through traditional microscopy, lipofuscins are readily observed as fluorescent granules thought to accumulate in lysosomes. However, lipofuscin granule formation and accumulation in senescent cells are poorly understood. Thus, this study examined lipofuscin accumulation in human fibroblasts exposed to various stressors. Our results substantiate that in glucose-starved or replicative senescence cells, where elevated oxidative stress levels activate autophagy, lipofuscins predominately appear as granules that co-localize with autolysosomes due to lysosomal acidity or impairment. Meanwhile, autophagosome formation is attenuated in cells experiencing oxidative stress induced by a doxorubicin pulse and chase, and lipofuscin fluorescence granules seldom manifest in the cytoplasm. As Torin-1 treatment activates autophagy, granular lipofuscins intensify and dominate, indicating that autophagy activation triggers their accumulation. Our results suggest that high oxidative stress activates autophagy but fails in lipofuscin removal, leaving an abundance of lipofuscin-filled impaired autolysosomes, referred to as residual bodies. Therefore, future endeavors in treating lipofuscin pathology-associated diseases and dysfunctions through autophagy activation demand meticulous consideration.
Keywords: autophagy; cellular senescence; lipofuscin.
이 논문은 세포 노화와 조직 노화 동안 축적되는 산화된 지질과 단백질 복합체인 리포푸신 과립의 축적이 자가포식 활성화에 의해 촉진된다는 것을 새로이 규명하여, 노화의 잘 알려진 생체 마커인 리포푸신 축적에 대한 새로운 시각을 제시한 논문입니다.
4. Mol. Cells 2023; 46(7), 451-460
Molecular Basis of Hexanoic Acid Taste in Drosophila melanogaster
Roshani Nhuchhen Pradhan, Bhanu Shrestha, Youngseok Lee
Animals generally prefer nutrients and avoid toxic and harmful chemicals. Recent behavioral and physiological studies have identified that sweet-sensing gustatory receptor neurons (GRNs) in Drosophila melanogaster mediate appetitive behaviors toward fatty acids. Sweet-sensing GRN activation requires the function of the ionotropic receptors IR25a, IR56d, and IR76b, as well as the gustatory receptor GR64e. However, we reveal that hexanoic acid (HA) is toxic rather than nutritious to D. melanogaster. HA is one of the major components of the fruit Morinda citrifolia (noni). Thus, we analyzed the gustatory responses to one of major noni fatty acids, HA, via electrophysiology and proboscis extension response (PER) assay. Electrophysiological tests show this is reminiscent of arginine-mediated neuronal responses. Here, we determined that a low concentration of HA induced attraction, which was mediated by sweet-sensing GRNs, and a high concentration of HA induced aversion, which was mediated by bitter-sensing GRNs. We also demonstrated that a low concentration of HA elicits attraction mainly mediated by GR64d and IR56d expressed by sweet-sensing GRNs, but a high concentration of HA activates three gustatory receptors (GR32a, GR33a, and GR66a) expressed by bitter-sensing GRNs. The mechanism of sensing HA is biphasic in a dose dependent manner. Furthermore, HA inhibit sugar-mediated activation like other bitter compounds. Taken together, we discovered a binary HA-sensing mechanism that may be evolutionarily meaningful in the foraging niche of insects.
Keywords: Drosophila melanogaster; gustatory receptor; hexanoic acid.
본 논문은 초파리가 헥사노익산의 맛을 인식하는 분자 수준의 새로운 메커니즘을 규명한 논문으로서 곤충의 먹이 탐색 행동을 이해하는 데 중요한 단서를 제공하며, 향후 해충 관리 전략 개발에 기여할 수 있습니다.
본 기사는 네티즌에 의해 작성되었거나 기관에서 작성된 보도자료로, BRIC의 입장이 아님을 밝힙니다. 또한 내용 중 개인에게 중요하다고 생각되는 부분은 사실확인을 꼭 하시기 바랍니다.
BRIC(ibric.org) Bio통신원(Molecules and Cells) 등록일2024.06.25