Article
Biochemistry & Molecular Biology
J. Allombert, C. Jaboulay, C. Michard, C. Andrea, X. Charpentier, A. Vianney, P. Doublet
Summary: The Legionella pneumophila Icm/Dot T4SS can translocate a large number of effectors, and research has found that their delivery is controlled by specific timing to effectively manipulate host cells. The timed delivery of effectors depends not only on chaperone protein interactions but also involves cyclic-di-GMP signaling.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biology
Michael J. Sheedlo, Clarissa L. Durie, Jeong Min Chung, Louise Chang, Jacquelyn Roberts, Michele Swanson, Dana Borden Lacy, Melanie D. Ohi
Summary: This passage discusses the relationship between Legionella pneumophila and Legionnaires' disease, as well as the structure of the Dot/Icm T4SS core complex determined by single particle cryo-EM. It identifies new proteins contributing to the core T4SS structure and defines two areas of symmetry mismatch.
Article
Biochemistry & Molecular Biology
Li Kang, Yujie Liu, Jianzhong He, Yaling Wang, Mengyang Xue, Xin Wu, Zhen Wang, Yunpeng Zhang, Manyu Chu, Jialun Li, Wei Wei, Jiwen Li, Enmin Li, Lujian Liao, Jianru Xiao, Rong Zhang, Liyan Xu, Jiemin Wong
Summary: By screening a small-molecule kinase inhibitor library, GSK3 ss was identified as a critical kinase for promoting the overexpression of SOX2 in ESCC. Inhibition of GSK3 ss selectively impaired the proliferation and stemness of SOX2-positive ESCC cells. Clinical studies also showed a positive correlation between GSK3 ss and SOX2 protein levels in esophageal tumors, indicating the potential of targeting GSK3 ss for the treatment of ESCC.
Review
Immunology
Tomoe Kitao, Tomoko Kubori, Hiroki Nagai
Summary: This review summarizes recent advances in the structural studies of the L. pneumophila IVB secretion system and provides insights into substrate recognition and transport mechanisms.
MICROBIOLOGY AND IMMUNOLOGY
(2022)
Article
Immunology
Ines P. Monteiro, Sofia Sousa, Vitor Borges, Paulo Goncalves, Joao Paulo Gomes, Luis Jaime Mota, Irina S. Franco
Summary: Two novel effectors, VFX05045 and VFX10045, of Legionella pneumophila were identified and their subcellular localizations were determined. Furthermore, the essential residues for nuclear targeting of VFX10045 were identified.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Dermatology
Kyung-Il Kim, Kyung Eun Jung, Young-Bin Shin, Chang-Deok Kim, Tae-Jin Yoon
Summary: In this study, we conducted a large-scale screening test on drugs approved for other diseases to find pigmentation-modulating agents. Among the potential drugs, sorafenib was selected for further investigation on its effect on pigmentation in melanoma cells. The results showed that sorafenib promoted pigmentation by increasing the melanin content and tyrosinase activity. Mechanistic studies revealed that this effect was mediated by the activation of beta-catenin signaling through the regulation of GSK3 beta phosphorylation.
EXPERIMENTAL DERMATOLOGY
(2022)
Article
Oncology
Kristina Y. Aguilera, Thuc Le, Rana Riahi, Anna R. Lay, Stefan Hinz, Edris A. Saadat, Ajay A. Vashisht, James Wohlschlegel, Timothy R. Donahue, Caius G. Radu, David W. Dawson
Summary: This study found that autophagy and lysosomal activity are enhanced in RNF43-mutant PDAC in response to PORCNi LGK974, which disrupts mitochondrial function and alters transcriptional activity. These findings reveal potential therapeutic targets for combining PORCNi with other drugs for the treatment of PDAC.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Sun Cheol Park, So Yeon Cho, Tae Hee Kim, Kyung Yeol Ko, Wan Seok Song, Seung Goo Kang, Geun-Shik Lee, Sung-il Yoon
Summary: LegK7 is an atypical kinase that activates through interaction with the host MOB1 protein without the need for phosphorylation. Upon binding with MOB1, LegK7 undergoes a structural reshaping that allows it to adopt a closed conformation compatible with ATP binding.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yao Zhang, Tingwang Shi, Yaohua He
Summary: The expression of GPR35 in bone marrow mesenchymal stem cells is suppressed in osteoporosis patients and mice, affecting osteogenic differentiation. GPR35 deficiency impairs the function of BMSCs, while overexpression contributes to osteogenesis. The synthetic GPR35 agonist zaprinast can reduce bone loss and promote bone generation, suggesting a potential novel treatment for osteoporosis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Fisheries
Yan Wang, Zhihong Liu, Xi Chen, Liqing Zhou, Xiujun Sun, Tao Yu, Xiaomei Wang, Yanxin Zheng, Biao Wu
Summary: Glycogen, an important energy form for aquatic shellfish, contributes to the flavor and quality of oysters. In this study, the genes GYS and GSK3 beta were identified and their functions in glycogen synthesis were explored. The expression of GYS was positively correlated with glycogen content, while the expression of GSK3 beta was negatively correlated. Knockdown of GSK3 beta reduced GYS expression, indicating its negative regulatory effect.
Article
Microbiology
Desiree Boeck, Dario Huesler, Bernhard Steiner, Joao M. Medeiros, Amanda Welin, Katarzyna A. Radomska, Wolf-Dietrich Hardt, Martin Pilhofer, Hubert Hilbi
Summary: Legionella pneumophila, the causative agent of Legionnaires' disease, uses a type IV secretion system (T4SS) to translocate effector proteins into host cells and form Legionella-containing vacuoles (LCV). Research shows that a significant portion of L. pneumophila bacteria tether their cell poles to the LCV membrane, facilitating the establishment of contact sites between T4SS and the LCV membrane. This study provides new insights into the interactions between L. pneumophila T4SS and the LCV membrane.
Article
Biochemistry & Molecular Biology
Eleonora Vecchio, Nancy Nistico, Gaetanina Golino, Enrico Iaccino, Domenico Maisano, Selena Mimmi, Annamaria Aloisio, Maurizio Renna, Angelica Avagliano, Alessandro Arcucci, Giuseppe Fiume, Ileana Quinto
Summary: The IBTK gene encodes the IBtk alpha protein, which plays a role in the regulation of MYC-dependent B-lymphomagenesis. Mechanistically, IBtk alpha indirectly activates the beta-catenin-dependent transcription of the MYC gene by modulating GSK3 beta. Silencing IBtk alpha leads to downregulation of MYC expression and increased apoptosis in Burkitt's lymphoma cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Sang Hyun Seo, Kyung Joo Cho, Hye Jung Park, Hye Won Lee, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Jae Hee Cheon, Jong In Yook, Man-Deuk Kim, Dong Jin Joo, Seung Up Kim
Summary: This study found that DKK1 is overexpressed in patients with hepatocellular carcinoma (HCC), and inhibiting DKK1 can enhance the anti-tumor efficacy of sorafenib in HCC. By regulating the activity of GSK3 beta and inhibiting the PI3K/Akt and Wnt/β-catenin pathways, a new therapeutic strategy for HCC has been identified.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Medicine, Research & Experimental
Yudong Fang, Bohan Chen, Zhangsuo Liu, Athena Y. Gong, William T. Gunning, Yan Ge, Deepak Malhotra, Amira F. Gohara, Lance D. Dworkin, Rujun Gong
Summary: Kidney aging is a challenge due to increased life expectancy, but targeting glycogen synthase kinase 3 beta (GSK3 beta) may delay this process by modulating senescence signaling in podocytes.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Immunology
Jing Wen, Xin Li, Qing-Xia Zhao, Xiao-Fan Yang, Meng-Li Wu, Qihong Yan, Junbiao Chang, Haikun Wang, Xia Jin, Xiao Su, Kai Deng, Ling Chen, Jian-Hua Wang
Summary: In this study, the researchers identified the Wnt downstream beta-catenin/TCF1 pathway as a crucial modulator for HIV-1 latency. Activation of this pathway with GSK3 inhibitors effectively promoted HIV-1 proviral DNA transcription and reactivated latency in CD4(+) T cells.
EMERGING MICROBES & INFECTIONS
(2022)