Article
Biochemistry & Molecular Biology
Agnieszka T. Kawashima, Cassandra Wong, Gema Lorden, Charles C. King, Pablo Lara-Gonzalez, Arshad Desai, Anne-Claude Gingras, Alexandra C. Newton
Summary: PHLPP1 is a tumor suppressor protein that is dynamically regulated in a cell cycle-dependent manner, with its N-terminal extension (NTE) being hyperphosphorylated by Cdk1 during mitosis. This phosphorylation regulates its binding to mitotic proteins, such as KNL1 and TPX2, potentially playing a role in its tumor-suppressive function.
MOLECULAR AND CELLULAR BIOLOGY
(2021)
Review
Oncology
Xinhang Xia, Wenhu Pi, Meng Chen, Wei Wang, Danyang Cai, Xuequan Wang, Yanli Lan, Haihua Yang
Summary: This review provides a brief overview of the history and structure of PHLPPs, and summarizes their emerging roles in lung cancer, including the regulation of signaling pathways, regulatory factors, disease prognosis, and treatment response. Therefore, PHLPPs can be considered as biomarkers or prognostic markers for lung cancer treatment.
FRONTIERS IN ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
Timothy R. Baffi, Ksenya Cohen-Katsenelson, Alexandra C. Newton
Summary: While protein kinases have been successfully targeted for diseases, protein phosphatases have not been utilized as therapeutic targets due to incomplete understanding of their effects on signaling networks. PHLPP, a relatively new player in cell signaling, has roles in cell survival, proliferation, and apoptosis, and recent research suggests it may have opposing effects in promoting cell survival. Additionally, PHLPP has been identified as a critical mediator of transcriptional programs in cancer and inflammation.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
(2021)
Article
Cell Biology
Martina Tufano, Laura Marrone, Chiara D'Ambrosio, Valeria Di Giacomo, Simona Urzini, Yichuan Xiao, Monica Matuozzo, Andrea Scaloni, Maria Fiammetta Romano, Simona Romano
Summary: FKBP51 is crucial for the survival of cancer cells, especially melanoma. It involved in various signaling pathways and forms a complex with Akt and PHLPP, known for dephosphorylation of Akt. This study focuses on the regulation of Akt activation by canonical and spliced isoforms of FKBP51. The TPR domain of FKBP51 is found to mediate Akt ubiquitination at K63, an important step for Akt activation. Surprisingly, PHLPP does not promote Akt phosphorylation when silenced and even induces Akt phosphorylation when overexpressed. PHLPP stabilizes TRAF6, an E3 ubiquitin ligase, and supports K63-ubiquitination of Akt. The interactome profile of FKBP51 in melanoma cells emphasizes the crucial role of PHLPP in enhancing oncogenic characteristics, particularly cell proliferation.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Kellie A. Lemoine, Julianna M. Fassas, Shirag H. Ohannesian, Nicole H. Purcell
Summary: PHLPP is a family of enzymes consisting of two isoforms (PHLPP1 and PHLPP2) that modulate intracellular activity by dephosphorylating specific residues on proteins like Akt. Dysregulation of PHLPP has been linked to various diseases, so targeting specific isoforms of PHLPP could be beneficial in treating cardiovascular diseases.
CELLULAR SIGNALLING
(2021)
Article
Neurosciences
Ayan Mallick, Medha Sharma, Chinmoy Sankar Dey
Summary: This review summarizes the current knowledge of PHLPP1 and PHLPP2, highlighting their crucial roles in the neuronal system and their associations with various diseases. It provides important insights for the development of future therapeutic strategies.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2022)
Article
Oncology
Wei Wang, Xinhang Xia, Kuifei Chen, Meng Chen, Yinnan Meng, Dongqing Lv, Haihua Yang
Summary: PHLPP, a potential tumor suppressor, is found to be a key regulator of sensitivity to EGFR-TKIs in NSCLC. Loss of PHLPP function leads to activation of survival pathways, reducing sensitivity to EGFR-TKIs. Enhancing PHLPP expression may be a valuable strategy for delaying or overcoming EGFR-TKIs drug resistance.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Medha Sharma, Chinmoy Sankar Dey
Summary: The study determines the role of individual PHLPP isoforms in insulin signaling and insulin resistance in neuronal cells. The results show that overexpressed and elevated endogenous expression of PHLPP isoforms under insulin resistant condition affect neuronal glucose uptake, while silencing Scribble increases glucose uptake.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Cell Biology
Hui Li, Bingxin Guan, Sen Liu, Haiting Liu, Lin Song, Guohao Zhang, Ruinan Zhao, Chengjun Zhou, Peng Gao
Summary: Gastric cancer is a highly heterogeneous disease with poor prognosis. Protein tyrosine phosphatases, specifically PTPN14, play a vital role in gastric cancer by promoting cell proliferation, migration, and invasion.
CELL DEATH & DISEASE
(2023)
Article
Pharmacology & Pharmacy
Wei Lei, Yiqi Yan, Yaolei Ma, Min Jiang, Boli Zhang, Han Zhang, Yuhong Li
Summary: This study investigated the cardioprotective mechanism of notoginsenoside R1 (NGR1) in improving ischemic heart diseases. The results showed that NGR1 improved echocardiographic, tissue pathological, and serum biochemical perturbations in myocardial ischemic rats. Network pharmacology studies indicated that NGR1 mainly regulated smooth muscle cell proliferation, vasculature development, and lipid metabolism signaling. Myocardial proteomics revealed that NGR1 focused on regulating metabolic and energy supply processes. The study demonstrated that NGR1 modulated lipid metabolism in ischemic myocardia by interacting with mTOR and AKT.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Deng-Ke Li, Xing-Rui Chen, Li-Na Wang, Jia-Hong Wang, Yue-Ting Wen, Zi-Ying Zhou, Ji-Ke Li, Jing-Xian Liu, Lin-Bo Cai, Shui-Sheng Zhong, Xiao-Ming Lyu, Faleti Oluwasijibomi Damola, Min-Ying Li, Jing-Jing Zhang, Yu-Mei Zeng, Qian-Li Wang, Qian-Bing Zhang, Hao Lyu, Xiao-Yan Fu, Wei Wang, Xin Li, Zhong-Xi Huang, Kai-Tai Yao
Summary: This study reveals the association between EBV and LN metastasis in NPC and demonstrates that EBV infection promotes cancer-associated lymphangiogenesis and LN metastasis. By regulating PHLPP1/p-AKT/HIF1a/VEGF-C, EBV induces lymphangiogenesis in NPC, providing a new therapeutic target for NPC with lymphatic metastasis.
MOLECULAR CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Travis C. Jackson, Cameron Dezfulian, Vincent A. Vagni, Jason Stezoski, Keri Janesko-Feldman, Patrick M. Kochanek
Summary: This study evaluated the neuroprotective effects of several unexplored PHLPP inhibitors and found that NSC74429 has neuroprotective effects across multiple injury mechanisms. Further research and optimization of drug dosing are necessary.
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
Chemistry, Analytical
Yan Wang, Ying Yan, Xinfa Liu, Changbei Ma
Summary: This study developed a simple and fast method to detect alkaline phosphatase quantitatively, with a LOD of 0.0098 U/L. The turn-off strategy allows for the detection of alkaline phosphatase presence, making it a potential tool for quantitative detection in clinical diagnosis.
Article
Spectroscopy
Yan Wang, Zhenwei Tang, Xueling Shang, Ying Yan, Xinying Xiang, Changbei Ma
Summary: In this study, a novel method for alkaline phosphatase (ALP) analysis based on Pb2+ dependent DNAzyme was described. By modifying the DNAzyme sequence and introducing exonuclease I, ALP analysis was successfully achieved with reduced background noise. The method exhibited a low detection limit and a wide linear range, and showed excellent performance in practical applications.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2022)
Article
Cardiac & Cardiovascular Systems
David E. Ebeid, Farid G. Khalafalla, Kathleen M. Broughton, Megan M. Monsanto, Carolina Y. Esquer, Veronica Sacchi, Nirmala Hariharan, Kelli Korski, Maryam Moshref, Jacqueline Emathinger, Christopher T. Cottage, Pearl J. Quijada, Jonathan H. Nguyen, Roberto Alvarez, Mirko Volkers, Mathias H. Konstandin, Bingyan J. Wang, Fareheh Firouzi, Julian M. Navarrete, Natalie A. Gude, Marie-Jose Goumans, Mark A. Sussman
Summary: Pim1 maintains telomere lengths in cardiomyocytes by inhibiting phosphorylation of the TGF beta pathway downstream effectors Smad2 and Smad3, which prevents repression of telomerase reverse transcriptase.
CARDIOVASCULAR RESEARCH
(2021)
Editorial Material
Cardiac & Cardiovascular Systems
Megan M. Monsanto, Fareheh Firouzi, Mark A. Sussman
CARDIOVASCULAR RESEARCH
(2021)
Article
Engineering, Biomedical
Jaeyeaon Cho, Sangsung Kim, Hyein Lee, Woongchan Rah, Hee Cheol Cho, Nam Kyun Kim, Seongho Bae, Dong Hoon Shin, Min Goo Lee, In-Hyun Park, Yoshiaki Tanaka, Eric Shin, Hong Yi, Ji Woong Han, Patrick Tae Joon Hwang, Ho-Wook Jun, Hun-Jun Park, Kyuwon Cho, Sang Wook Lee, Jae Kyung Jung, Rebecca D. Levit, Mark A. Sussman, Richard P. Harvey, Young-sup Yoon
Summary: The direct reprogramming of mouse fibroblasts into cardiomyocytes, endothelial cells, and smooth muscle cells to form cardiac tissue structures improved cardiac function when implanted into infarcted mouse hearts.
NATURE BIOMEDICAL ENGINEERING
(2021)
Review
Cardiac & Cardiovascular Systems
Oscar Echeagaray, Clarissa Savko, Andrea Gallo, Mark Sussman
Summary: This review summarizes the cardiovascular consequences of vaping and highlights the importance of research in this area. Recent findings indicate that vaping can have an impact on cardiovascular homeostasis, inflammation, and molecular changes, suggesting potential health issues associated with vaping and the need for further investigation into the pathogenesis.
CURRENT OPINION IN CARDIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Oscar Echeagaray, Taeyong Kim, Alex Casillas, Megan Monsanto, Mark Sussman
Summary: Ex vivo expansion of cells is crucial in regenerative medicine to generate large populations for therapeutic use. The adaptation to culture conditions leads to increased transcriptome diversity and decreased population heterogeneity in cKit+ cardiac interstitial cells (cCICs). The transcriptional profiles of cells from different origins, such as neonatal versus adult tissue, show contrasting imprint of age influence on cell cycle, senescence, RNA transport, and ECM-receptor/fibrosis pathways.
Article
Biology
Carolina Esquer, Oscar Echeagaray, Fareheh Firouzi, Clarissa Savko, Grant Shain, Pria Bose, Abigail Rieder, Sophie Rokaw, Andrea Witon-Paulo, Natalie Gude, Mark A. Sussman
Summary: Vaping of flavored liquids can lead to pulmonary injury, with profound pathological changes in upper airway, lung tissue, and cellular structure. This study also highlights the potential transcriptional reprogramming and impaired cardiac function associated with vaping.
LIFE SCIENCE ALLIANCE
(2022)
Review
Pharmacology & Pharmacy
Mark A. Sussman
Summary: Modern vaping, a rapidly growing industry, has raised concerns about its impact on human health, particularly on the lungs and cardiopulmonary system. Studies are urgently needed to understand the biological effects of vaping and develop strategies to mitigate the associated harmful effects.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Cardiac & Cardiovascular Systems
Kathleen Broughton, Carolina Esquer, Oscar Echeagaray, Fareheh Firouzi, Grant Shain, David Ebeid, Megan Monsanto, Dena Yaareb, Leila Golgolab, Natalie Gude, Mark A. Sussman
Summary: This study reveals that surface Lin28A serves as a marker for oxidative stress in cardiac interstitial cells (CICs) and its expression can be antagonized by antioxidant treatment. The altered localization of Lin28A is associated with senescence markers and oxidative stress pathways in CICs. These findings provide important insights into the mechanisms of cardiac stress and aging.
CARDIOVASCULAR RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Fareheh Firouzi, Oscar Echeagaray, Carolina Esquer, Natalie A. Gude, Mark A. Sussman
Summary: The heterogeneity and plasticity of cardiac fibroblast population pose challenges for the study of cardiac biology and intervention strategies. This study evaluates the role of c-Kit biology within the population of cardiac fibroblasts, providing a fundamental basis for future research.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Kathleen M. Broughton, Carolina Esquer, Oscar H. Echeagaray, Fareheh Firouzi, Grant Shain, David Ebeid, Megan M. Monsanto, Dena Yaareb, Leila Golgolab, Natalie A. Gude, Mark A. Sussman
Meeting Abstract
Cardiac & Cardiovascular Systems
Mark A. Sussman, Clarissa Savko, Pria Bose, Sophie Rokaw, Abbie Rieder, Taha Alani, Tyler Hopkins, Carolina Esquer, Grant Shain
CIRCULATION RESEARCH
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Oscar E. Echeagaray, Taeyong Kim, Alex Casillas, Megan M. Monsanto, Mark A. Sussman
Meeting Abstract
Cardiac & Cardiovascular Systems
Fareheh Firouzi, Oscar H. Echeagaray, Carolina Y. Esquer, Natalie A. Gude, Mark A. Sussman
Meeting Abstract
Cardiac & Cardiovascular Systems
Fareheh Firouzi, Oscar H. Echeagaray, Carolina Y. Esquer, Natalie A. Gude, Mark A. Sussman
CIRCULATION RESEARCH
(2021)
Meeting Abstract
Cardiac & Cardiovascular Systems
Mark A. Sussman, Carolina Esquer, Clarissa Savko, Grant Shain, Oscar E. Echeagaray, Fareheh Firouzi, Pria Bose, Abbie Rieder, Sophie Rokaw, Andrea Witon-Paulo, Natalie A. Gude
CIRCULATION RESEARCH
(2021)