Article
Multidisciplinary Sciences
Leire Torices, Caroline Nunes-Xavier, Jose I. Lopez, Rafael Pulido
Summary: PTEN is a tumor suppressor gene frequently mutated in human tumors, and its mutations are the diagnostic marker for PTEN Hamartoma Tumor Syndrome (PHTS), a disorder characterized by multiple hamartomas, cancer predisposition, and neurodevelopmental alterations. This study generated and characterized anti-PTEN monoclonal antibodies recognizing the PTEN C2-domain, which can be used to study the expression and function of PTEN isoforms and mutations associated with disease. These antibodies are suitable for investigating the pathogenicity of PTEN C-terminal truncations that have lost the PTEN C-terminal epitopes but retain stability and function.
Article
Multidisciplinary Sciences
Motoki Ono, Tsutomu Miyamoto, Ryoichi Asaka, Junko Uchikawa, Hirofumi Ando, Yasuhiro Tanaka, Manaka Shinagawa, Yusuke Yokokawa, Shiho Asaka, Tian-Li Wang, Ie-Ming Shih, Tanri Shiozawa
Summary: This study aimed to create an EAOC mouse model by transplanting uterine pieces from donor mice, in which Arid1a and/or Pten was conditionally knocked out in endometrial cells, onto the ovarian surface or peritoneum of recipient mice. The results showed that induction of only Pten KO evoked atypical endometriosis, while induction of Arid1a; Pten double-KO evoked structures similar to EAOC. This mouse model provides a useful tool for investigating the mechanisms underlying the development of EAOC.
SCIENTIFIC REPORTS
(2023)
Article
Immunology
Danyang He, Heping Xu, Huiyuan Zhang, Ruihan Tang, Yangning Lan, Ruxiao Xing, Shaomin Li, Elena Christian, Yu Hou, Paul Lorello, Barbara Caldarone, Jiarui Ding, Lan Nguyen, Danielle Dionne, Pratiksha Thakore, Alexandra Schnell, Jun R. Huh, Orit Rozenblatt-Rosen, Aviv Regev, Vijay K. Kuchroo
Summary: This study reveals that cellular metabolism regulates microglial function during neurodevelopment. The IL-33 signaling axis, coupled with AKT activity, promotes mitochondrial metabolism and phagocytic function in microglia. This microglia-astrocyte circuit plays a crucial role in the metabolic adaptation and phagocytic function of microglia during early development.
Article
Oncology
Xuxiao Chen, Ao Huang, Yupeng Wang, Feiyu Chen, Bo Hu, Xin Zhang, Yunfan Sun, Jian Wang, Jianwen Cheng, Pengxiang Wang, Yuan Ji, Shuangjian Qiu, Jia Fan, Jian Zhou, Xinrong Yang
Summary: BAP1 and its mutations have been shown to play critical roles in tumor biology, particularly in hepatocellular carcinoma (HCC). This study found that mutations and downregulation of BAP1 were associated with aggressive tumor phenotypes in HCC, while wild-type BAP1 inhibited HCC cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) by stabilizing PTEN through deubiquitination. These findings suggest that BAP1 acts as a tumor suppressor in HCC by regulating PTEN and EMT.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Cell Biology
Jose Antonio Ma. G. Garrido, Krizelle Mae M. Alcantara, Joshua Miguel C. Danac, Fidel Emmanuel C. Serrano, Eva Maria de la Paz, Reynaldo L. Garcia
Summary: PTEN is a well-characterized tumor suppressor with both lipid and protein phosphatase activities. Mutations in PTEN may not only affect protein function but also interactions with downstream effectors, leading to variable oncogenic readouts. Further mechanistic studies are needed to determine the differential oncogenic potencies of these mutants.
Article
Oncology
Yufeng Dine, Honggang Chi, Jialiang Shao, Tiezhu Sh, Hua Yu, Xiang Wan, Xiongjun Wang
Summary: The acetylation of K620 on the extracellular domain of LIFR is shown to be a promising biomarker for monitoring PCa progression, as it enhances the homodimerization of LIFR and activates various signaling pathways.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Yanlin Yu, Meng Dai, Liping Huang, Weiping Chen, Ellen Yu, Arnulfo Mendoza, Helen Michael, Chand Khanna, Marcus Bosenberg, Martin McMahon, Glenn Merlino
Summary: This study found that PTEN expression negatively correlates with the metastatic progression of melanoma. Wildtype PTEN expression inhibits melanoma cell invasiveness and metastasis in a dose-dependent manner, which specifically requires PTEN protein phosphatase activity. PTEN phosphatase activity inhibits metastasis by regulating the Entpd5/IGF1R pathway through ATF6.
Article
Multidisciplinary Sciences
Florent Peglion, Lavinia Capuana, Isabelle Perfettini, Laurent Boucontet, Ben Braithwaite, Emma Colucci-Guyon, Emie Quissac, Karin Forsberg-Nilsson, Flora Llense, Sandrine Etienne-Manneville
Summary: Loss of PTEN promotes cell migration while targeting AMPK activity can counteract this effect. This suggests the important regulatory roles of PTEN and AMPK in tumor invasion and provides new therapeutic opportunities for glioblastoma.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Samia Kadri, Kumiko Nakada-Tsukui, Natsuki Watanabe, Ghulam Jeelani, Tomoyoshi Nozaki
Summary: The study characterized the major PTEN in Entamoeba histolytica, EhPTEN1, and found its crucial role in regulating endocytosis, phagocytosis, cell migration, and proliferation in this parasite.
Article
Biochemistry & Molecular Biology
Christian Bassi, Jerome Fortin, Bryan E. Snow, Andrew Wakeham, Jason Ho, Jillian Haight, Annick You-Ten, Emily Cianci, Luke Buckler, Chiara Gorrini, Vuk Stambolic, Tak W. Mak
Summary: The tumor suppressor gene PTEN is frequently mutated in various cancers, and its phosphorylation by ATM plays a critical role in apoptosis, genomic stability, and tumorigenesis. The PTEN-398A mutation accelerates tumor formation in HER2-positive breast cancer by disrupting the S phase checkpoint controlled by the PI3K-p27(Kip1)-CDK2 axis, leading to DNA damage accumulation and decreased apoptosis. Defects in PTEN-398A protein relocalization to the plasma membrane in response to genotoxic stress contribute to these effects.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Jian-Hua Luo, Silvia Liu, Junyan Tao, Bao-Guo Ren, Katherine Luo, Zhang-Hui Chen, Michael Nalesnik, Kathleen Cieply, Tianzhou Ma, Shi-Yuan Cheng, Qi Chen, George K. Michalopoulos, Joel B. Nelson, Rohit Bhargava, Jun Zhang, Deqin Ma, David Jarrard, Arjun Pennathur, James D. Luketich, Donald B. DeFranco, Satdarshan Paul Monga, George Tseng, Yan-Ping Yu
Summary: The fusion gene Pten-NOLC1, derived from Pten gene, is a driver for human cancers as it promotes cancer proliferation, growth, invasion, and metastasis. Its presence in primary cancer samples and cancer cell lines from different organs suggests its significance in oncogenesis.
Article
Biochemistry & Molecular Biology
Luyang Han, Yuting Wu, Fangming Liu, Hongbing Zhang
Summary: The aberrant activation of the mTOR signaling pathway can lead to tumor growth by stimulating translation initiation and protein synthesis. This study investigated the potential of eFT226, a selective inhibitor of eIF4A-mediated translation, in treating mTOR hyperactive cells caused by the deletion of TSC1/2 or PTEN. Results showed that eFT226 effectively inhibited the proliferation of Tsc2- and Pten-deficient cells by inducing necroptosis and G2/M phase arrest. Additionally, eFT226 blocked the development of TSC2-deficient tumors. Overall, these findings suggest that eFT226, as a translation initiation inhibitor, holds promise in the treatment of hyperactive mTOR-mediated tumors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Barbara Seliger, Chiara Massa
Summary: A better understanding of the molecular mechanisms underlying resistance to immunotherapy is needed to improve its efficacy. Activation of oncogenic pathways and inactivation of tumor suppressor genes in tumor cells can inhibit immune cell recognition and affect the composition of the tumor microenvironment, leading to impaired anti-tumoral immune response.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Wenfeng Hua, Na Jiang, Yifei Wu, Cailian Zhou, Kequan Chen, Xin Wang
Summary: This study constructed three in vivo NMN synthesis pathways based on the supply of co-substrate PRPP. By optimizing the conditions, a yield of 1.8 mM NMN was obtained. The research provides important theoretical and practical evidence for the application of NMN in the field of anti-aging.
Review
Physiology
Tianyu He, Xiaoyun Zhang, Jianyu Hao, Shigang Ding
Summary: The PTEN gene is a crucial tumor suppressor gene with diverse biological functions, playing important roles in cell morphology, proliferation, differentiation, and other processes. While well-documented in malignant tumors of the digestive system, PTEN may also be involved in benign processes and non-neoplastic diseases of the digestive tract. Recent discoveries of PTEN isoforms hold promise for understanding its broader biological effects in non-neoplastic digestive diseases.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Valerie T. Ressler, Kalie A. Mix, Ronald T. Raines
ACS CHEMICAL BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Emily R. Garnett, Jo E. Lomax, Bassem M. Mohammed, David Gailani, John P. Sheehan, Ronald T. Raines
Review
Biochemistry & Molecular Biology
Robert W. Newberry, Ronald T. Raines
ACS CHEMICAL BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Aubrey J. Ellison, I. Caglar Tanrikulu, Jesus M. Dones, Ronald T. Raines
Article
Biology
Lindsey R. F. Backman, Yolanda Y. Huang, Mary C. Andorfer, Brian Gold, Ronald T. Raines, Emily P. Balskus, Catherine L. Drennan
Article
Biochemistry & Molecular Biology
Henry R. Kilgore, Andrew P. Latham, Valerie T. Ressler, Bin Zhang, Ronald T. Raines
Article
Biochemistry & Molecular Biology
Nile S. Abularrage, Brian J. Levandowski, Ronald T. Raines
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Chemistry, Medicinal
Chelcie H. Eller, Ronald T. Raines
ACS INFECTIOUS DISEASES
(2020)
Article
Biochemical Research Methods
Jessica Sayers, Evans C. Wralstad, Ronald T. Raines
Summary: The ribonuclease S complex has led to historic discoveries in protein chemistry and enzymology, but its applications have been hindered by two main drawbacks: immune response in humans and susceptibility to dissociation. By semi-synthesizing an RNase S conjugate derived from human pancreatic ribonuclease and stabilized with a covalent interfragment cross-link, these limitations have been addressed, enabling unprecedented applications of the RNase-S system.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sayani Chattopadhyay, Leandro B. C. Teixeira, Laura L. Kiessling, Jonathan F. McAnulty, Ronald T. Raines
Summary: This study provides a method to upregulate the TGF-beta signaling pathway by clustering the extracellular domains of TGF-beta receptors, which can enhance wound healing.
ACS CHEMICAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Emily R. Garnett, Ronald T. Raines
Summary: Pancreatic-type ribonucleases (ptRNases) are a family of vertebrate-specific secretory endoribonucleases that catalyze the degradation of RNA substrates and mediate biological functions. Two ptRNases, RNase 1 and angiogenin, are known to be involved in inflammation, blood coagulation, neovascularization, cancer, amyotrophic lateral sclerosis, and cellular stress response. Further research is ongoing to elucidate the biology of these and other ptRNases.
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Infectious Diseases
Ian W. Windsor, Dawn M. Dudley, David H. O'Connor, Ronald T. Raines
Summary: By engineering amino acid substitutions in RNase 1, it has been transformed into a zymogen that can be activated by HIV-1 protease, showing high toxicity towards infected cells.
AIDS RESEARCH AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Linus B. Boll, Ronald T. Raines
Summary: The position of Cys in a protein sequence can be exploited to improve site-selectivity in maleimide-based modifications, while differences in the reactivity of Lys towards an NHS ester are modest.
Meeting Abstract
Biochemistry & Molecular Biology
Lindsey R. F. Backman, Yolanda Y. Huang, Mary C. Andorfer, Brian Gold, Ronald T. Raines, Emily P. Balskus, Catherine L. Drennan
Meeting Abstract
Biochemistry & Molecular Biology
Henry Ralph Kilgore, Valerie T. Ressler, Ronald T. Raines