Article
Biochemistry & Molecular Biology
Shu Wu, Yuanlong Ge, Kaixuan Lin, Qianqian Liu, Haoxian Zhou, Qian Hu, Yong Zhao, Weifeng He, Zhenyu Ju
Summary: This study reveals a novel function of telomerase RNA (TERC) in regulating cell proliferation through positive feedback regulation of the PI3K-AKT pathway. TERC activates the transcription of target genes from the PI3K-AKT pathway, and the activation of PI3K-AKT pathway induced by TERC also plays a critical role in the proliferation of CD4(+) T cells.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Cell Biology
Fan Bao, Peiqi Hao, Su An, Yang Yang, Ying Liu, Qian Hao, Mubashir Ejaz, Xiao-Xi Guo, Tian-Rui Xu
Summary: The phosphatidylinositol 3-kinase-Akt signaling pathway is crucial in regulating cell proliferation and apoptosis, with Akt kinase being a central player. Although Akt is frequently overexpressed in tumors, inhibiting it has significant clinical side effects, making it unsuitable for cancer treatment. Recent focus has shifted to Akt scaffold proteins as potential targets for cancer therapy, as they play a role in regulating Akt signaling specificity.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Editorial Material
Immunology
Jessica Buck, Nikhil S. Joshi
Summary: NFAT5 transcription factor regulates T cell exhaustion during cancer but not during chronic viral infection.
Article
Cell Biology
Tran Vinh Hong Nguyen, Ulrich Bergmann, Thomas Kietzmann, Daniela Mennerich
Summary: This study found that insulin stimulates the expression of HIF-3 alpha through the PKB signaling pathway under both normal and low oxygen conditions. The phosphorylation site identified in HIF-3 alpha plays a crucial role in its stability and cell migration, highlighting a novel mechanism by which insulin affects HIF-3 alpha expression and activity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Antonieta L. Salguero, Maggie Chen, Aaron T. Balana, Nam Chu, Hanjie Jiang, Brad A. Palanski, Hwan Bae, Katharine M. Wright, Sara Nathan, Heng Zhu, Sandra B. Gabelli, Matthew R. Pratt, Philip A. Cole
Summary: This study investigates the regulatory effects of phosphorylation of Tyr474 and O-GlcNAcylation of Ser473 on Akt, finding that both modifications can increase Akt's kinase activity toward substrates. Kinase assays using protein microarrays showed high similarity in the protein substrates phosphorylated by phosphoSer473 Akt and O-GlcNAcSer473 Akt. Two Akt substrates, PPM1H and NEDD4L, were validated in further solution-phase assays and cell transfection experiments.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Liang-Jian Chen, Na-Na Zhang, Chun-Xiang Zhou, Zhi-Xia Yang, Yan-Ru Li, Teng Zhang, Cong-Rong Li, Xin Wang, Yang Wang, Zi-Bin Wang, Zheng-Rong Xia, Zhen-Bo Wang, Cui-Lian Zhang, Yi-Chun Guan, Qing-Yuan Sun, Dong Zhang
Summary: This study reveals the critical role of Gm364 in female fertility, where its knockout results in decreased follicle numbers, impaired oocyte quality, reduced oocyte maturation, and increased aneuploidy. Mechanistically, Gm364 interacts with MIB2 to activate the Notch2-AKT signaling pathway, influencing oocyte meiosis and quality.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Mate Marosi, Miroslav N. Nenov, Jessica Di Re, Nolan M. Dvorak, Musaad Alshammari, Fernanda Laezza
Summary: In this study, it was found that Akt inhibition enhances peak transient Na+ current density through Na(v)1.6 channels and increases action potential firing in CA1 pyramidal neurons, accompanied by a decrease in action potential current threshold. Complementary confocal analysis revealed that Akt inhibition is associated with the lengthening of Na(v)1.6 fluorescent intensity along the axonal initial segment, providing a mechanism for augmented neuronal excitability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Ilenia Sana, Maria Elena Mantione, Piera Angelillo, Marta Muzio
Summary: In recent years, significant progress has been made in the clinical management of chronic lymphocytic leukemia and other B-cell malignancies by targeting B-cell receptor signaling molecules. However, a proportion of patients remain uncured, leading to efforts in studying new potential targets. NFAT is overexpressed and constitutively activated in CLL, with targeting this molecule impacting on CLL cell viability.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Lei Huang, Xiao-Ou Zhang, Esteban J. Rozen, Xiaomei Sun, Benjamin Sallis, Odette Verdejo-Torres, Kim Wigglesworth, Daniel Moon, Tingting Huang, John P. Cavaretta, Gang Wang, Lei Zhang, Jason M. Shohet, Mary M. Lee, Qiong Wu
Summary: The protein arginine methyltransferase 5 (PRMT5) regulates the expression of metastasis-related genes by methylating Akt protein, which is required for its phosphorylation and activation, leading to the upregulation of pro-metastatic transcription factors. Moreover, inhibiting PRMT5 can attenuate primary tumor growth and block metastasis in multiple organs, suggesting it may be a potential therapeutic target for high-risk metastatic cancers.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Jiro Sakai, Jiyeon Yang, Chao-Kai Chou, Wells W. Wu, Mustafa Akkoyunlu
Summary: Newborns have a lower humoral immune response than adults due to the immunoregulatory role of IL-10. This study found that both B-1 cells and non-B-1 cells in neonatal mice produce IL-10 in response to B cell antigen receptor (BCR) activation. The production of IL-10 is mediated by the activation of STAT5 and IL-6, and further activates STAT3. IL-10 secreted by neonatal non-B-1 cells can inhibit TNF-alpha secretion by macrophages.
Article
Multidisciplinary Sciences
Ying Wang, Jun Liu, Chizuru Akatsu, Runyun Zhang, Hai Zhang, Han Zhu, Kangwei Liu, Han-Ying Zhu, Qing Min, Xin Meng, Chaoqun Cui, Yue Tang, Meiping Yu, Yaxuan Li, Xiaoqian Feng, Hao Wei, Zichao Wen, Sihan Ji, Martin G. Weigert, Takeshi Tsubata, Ji-Yang Wang
Summary: BCR stimulation induces the upregulation of LAPTM5 expression, which triggers apoptosis of immature B cells through two pathways. LAPTM5 mediates BCR internalization and degradation of WWP2, leading to PTEN accumulation, AKT suppression, increased FOXO1 expression, and upregulation of cell cycle inhibitor p27Kip1 and proapoptotic molecule BIM, ultimately contributing to immature B cell apoptosis and B cell tolerance.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Iksen, Sutthaorn Pothongsrisit, Varisa Pongrakhananon
Summary: Lung cancer is a common and highly lethal cancer, posing a major clinical challenge. The PI3K/AKT/mTOR pathway has been linked to lung cancer, making it a significant therapeutic target. Interest in targeting these pathways with medications has grown, showing promise in various types of studies.
Article
Cell Biology
Mo Chen, Suyong Choi, Tianmu Wen, Changliang Chen, Narendra Thapa, Jeong Hyo Lee, Vincent L. Cryns, Richard A. Anderson
Summary: The study reveals a novel mechanism of interaction between nuclear p53 and the PI3K-AKT pathway, which is distinct from the canonical membrane-localized pathway. It shows that genotoxic stress activates nuclear AKT through a p53-dependent mechanism, leading to the inhibition of DNA damage-induced apoptosis. This finding highlights the therapeutic relevance of the nuclear p53-phosphoinositide signalosome, as it is insensitive to currently available PI3K inhibitors.
NATURE CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rodrigo P. Silva-Aguiar, Diogo B. Peruchetti, Lucas S. Florentino, Christina M. Takiya, Maria-Paz Marzolo, Wagner B. Dias, Ana Acacia S. Pinheiro, Celso Caruso-Neves
Summary: Renal proximal tubule cells regulate protein reabsorption through the phosphoinositide-3-kinase/protein kinase B pathway. Physiologic albumin concentration and PI3K/AKT pathway form a positive feedback loop, expanding endocytic capacity and adapting to physiological fluctuations in albumin filtration, preventing urinary excretion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Jose G. Miranda, Wolfgang E. Schleicher, Kristen L. Wells, David G. Ramirez, Samantha P. Landgrave, Richard K. P. Benninger
Summary: This study examines how patterns of electrical activity regulate NFAT activation, gene transcription, and islet function, and provides insights into how these factors are disrupted in diabetes.
MOLECULAR METABOLISM
(2022)