Article
Biochemistry & Molecular Biology
Alexandria L. Shaw, Matthew A. H. Parson, Linda Truebestein, Meredith L. Jenkins, Thomas A. Leonard, John E. Burke
Summary: Akt is a key regulator of cell growth signaling and its hyperactivation is oncogenic. This study used hydrogen deuterium exchange mass spectrometry to investigate the conformational changes induced by Akt inhibitors. The findings provide valuable insights for designing targeted therapeutics against Akt.
Article
Biochemistry & Molecular Biology
Adrian Perez-Ramos, Rabia Ladjouzi, Abdellah Benachour, Djamel Drider
Summary: This study focused on the biosynthetic pathway of the leaderless two-peptide bacteriocin EntDD14, revealing that proteins containing the PH domain, such as DdE and DdF, play a crucial role in the transport of EntDD14.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Tripti Shrestha Bhattarai, Tambudzai Shamu, Alexander N. Gorelick, Matthew T. Chang, Debyani Chakravarty, Elena Gavrila, Mark T. A. Donoghue, JianJong Gao, Swati Patel, Sizhi Paul Gao, Margaret H. Reynolds, Sarah M. Phillips, Tara Soumerai, Wassim Abida, David M. Hyman, Alison M. Schram, David B. Solit, Lillian M. Smyth, Barry S. Taylor
Summary: AKT mutations can affect downstream effector pathways and sensitivity to AKT inhibitors in different solid cancer types.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Sophie Sluysmans, Isabelle Mean, Lionel Jond, Sandra Citi
Summary: The localization of WW-PLEKHAs at specific subcellular sites is determined by the interaction of their different structural domains and multiple protein-lipid and protein-protein interactions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Junya Hasegawa, Yasunori Uchida, Kojiro Mukai, Shoken Lee, Tatsuyuki Matsudaira, Tomohiko Taguchi
Summary: Cells internalize proteins and lipids through endocytosis, maintaining a balance in the plasma membrane by replenishing through a recycling pathway. In addition to their role in recycling, recycling endosomes have been found to play unexpected roles in membrane traffic and cell signaling. This review highlights these emerging issues, particularly focusing on phosphatidylserine and the pathogenesis of Hermansky Pudlak syndrome type 2 related to dysregulated recycling endosome functions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Tatsunori Shimoi, Jun Hashimoto, Kazuki Sudo, Akihiko Shimomura, Emi Noguchi, Chikako Shimizu, Mayu Yunokawa, Kan Yonemori, Hiroshi Yoshida, Masayuki Yoshida, Tomoyasu Kato, Takayuki Kinoshita, Takahiro Fukuda, Yasuhiro Fujiwara, Kenji Tamura
Summary: The frequency of AKT1 mutations in Asian women with breast cancer and endometrial cancer is relatively low, at 7.4% and 4.1% respectively. AKT1 mutations are more common in HER2-negative breast cancer subtypes and in endometrial cancer with endometrioid histology. The frequencies of AKT1 mutations were similar between Asian and other regional women, and the predictive significance of these mutations in both tumor types is limited due to their low frequency.
Article
Biochemistry & Molecular Biology
Svenja Wiechmann, Benjamin Ruprecht, Theresa Siekmann, Runsheng Zheng, Martin Frejno, Elena Kunold, Thomas Bajaj, Daniel P. Zolg, Stephan A. Sieber, Nils C. Gassen, Bernhard Kuster
Summary: Through chemoproteomic target affinity profiling and phosphoproteomics, this study analyzed the mechanisms of action of five clinical AKT inhibitors in BT-474 breast cancer cells. The results indicated that these inhibitors mainly exert their therapeutic effects by regulating AKT substrates, expanding the known AKT signaling network. Additionally, novel AKT substrates related to mitosis, cytoskeleton organization, and autophagy were discovered.
ACS CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chiaki Murakami, Fumio Sakane
Summary: This study revealed that SMSr can generate DG by hydrolyzing PE, PA, PI, and PC without ceramide, and showed PAP and PI/PE/PC-PLC activities, forming a novel signaling pathway independent of the PI(4,5)P-2 cycle.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Naoyuki Kawase, Atsuya Sugihara, Kentaro Kajiwara, Michio Hiroshima, Kanako Akamatsu, Shigeyuki Nada, Kunio Matsumoto, Masahiro Ueda, Masato Okada
Summary: The CDCP1-SRC-ARHGEF7-RAC1 pathway plays a crucial role in HGF-induced invasion of a subset of breast cancer cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Madeline R. Sponholtz, Eric N. Senning
Summary: Using total internal reflection fluorescence microscopy, we observed the dissociation of GFP-tagged pleckstrin homology (PH) domains of AKT and PLC delta 1 from the plasma membranes of cells, and found that substantial rebinding events occurred in PLC delta 1-PH-GFP dissociation kinetics. By applying inositol triphosphate (IP3) during the unroofing process, we suppressed rebinding events significantly, indicating competitive action between IP3 and phosphatidylinositol 4,5-bisphosphate (PIP2) for the same binding site. Our discussion revolves around how free PIP2 levels modulate the interaction between membrane-associated proteins and the plasma membrane.
ACS CHEMICAL NEUROSCIENCE
(2021)
Review
Biochemical Research Methods
Qisheng Pan, Thanh Binh Nguyen, David B. Ascher, Douglas E. Pires
Summary: Changes in protein sequence can significantly impact protein folding, stability, and dynamics. Methods to estimate the effects of missense mutations on protein stability have been developed and validated using experimentally derived structures and biophysical measurements. However, the reliability of these methods in the absence of experimental structural data has not been systematically evaluated. This study investigates the performance and robustness of structural methods applied to homology models and highlights the limitations of these tools when sequence identity is low.
BRIEFINGS IN BIOINFORMATICS
(2022)
Review
Oncology
Yu Chen, Qingfan Yang, Jinrun Xu, Liyao Tang, Yan Zhang, Fukuan Du, Yueshui Zhao, Xu Wu, Mingxing Li, Jing Shen, Ruilin Ding, Hongying Cao, Wanping Li, Xiaobing Li, Meijuan Chen, Zhigui Wu, Chi Hin Cho, Yu Du, Qinglian Wen, Zhangang Xiao
Summary: PROTAC is a powerful strategy for targeted protein degradation, utilizing the ubiquitin-proteasome degradation system to induce protein degradation. It has advantages such as broad targeting profile, good cell permeability, tissue specificity, high selectivity, oral bioavailability, and controllability. Multiple PROTACs targeting gastrointestinal cancers have been successfully developed and validated in clinical trials.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Biophysics
Jackson Weako, Hyunbum Jang, Ozlem Keskin, Ruth Nussinov, Attila Gursoy
Summary: This study investigates the atomic-level interaction between CaM and Akt's PHD through modeling and molecular dynamics simulations, showing that the interaction is thermodynamically stable and involves a beta-strand instead of an alpha-helix. The polar head of PIP3 weakens the CaM-PHD interaction, suggesting a release mechanism at the plasma membrane.
BIOPHYSICAL JOURNAL
(2021)
Article
Biochemical Research Methods
Michelle Palmieri, Bruno Catimel, Dmitri Mouradov, Anuratha Sakthianandeswaren, Eugene Kapp, Ching-Seng Ang, Nicholas A. Williamson, Cameron J. Nowell, Michael Christie, Jayesh Desai, Peter Gibbs, Antony W. Burgess, Oliver M. Sieber
Summary: The nuclear translocation of PI3K alpha regulates the subcellular levels of PtdIns(3,4,5)P3 in colorectal cancer cell lines, and 867 potential nuclear PtdIns(3,4,5)P3 effector proteins have been identified. These effector proteins are mainly involved in RNA metabolism and may play a role in modulating pre-mRNA splicing. These findings suggest that nuclear PI3K alpha signaling through PtdIns(3,4,5)P3 effector proteins is important for CRC development.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Review
Oncology
Xin-Yuan Dai, Liang Shi, Zhi Li, Hai-Yan Yang, Ji-Fu Wei, Qiang Ding
Summary: N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNAs, installed by writers and erased by erasers, recognized by readers. YTH family proteins, as the first identified m6A reader proteins, play essential roles in cancer tumorigenesis through regulating RNA metabolism.
FRONTIERS IN ONCOLOGY
(2021)