Article
Biochemistry & Molecular Biology
Viktoria K. Ilic, Olga Egorova, Ernest Tsang, Milena Gatto, Yi Wen, Yong Zhao, Yi Sheng
Summary: The proto-oncogene MDM2 is frequently amplified in many human cancers and its overexpression is associated with poor prognosis. MDM2 shows oncogenic activity by negatively regulating tumor suppressor p53 and proteins involved in DNA repair, cell cycle control, and apoptosis pathways. Inhibition of MDM2 activity has been pursued as an attractive direction for anti-cancer therapeutics. This study identified a biflavonoid compound Hinokiflavone as a promising candidate compound targeting MDM2. Hinokiflavone was shown to bind the MDM2-MDMX RING domain and inhibit MDM2-mediated ubiquitination in vitro. Hinokiflavone treatment downregulated MDM2 and MDMX and induced apoptosis in various cancer cell lines. Hinokiflavone demonstrated tumor-suppressive activity that is both p53-dependent and -independent.
Article
Cell Biology
Xiaohua Huang, Bin Wang, Runji Chen, Shuping Zhong, Fenfei Gao, Yanmei Zhang, Yongdong Niu, Congzhu Li, Ganggang Shi
Summary: The study aimed to assess the mechanism of FXR in cervical cancer and found that FXR reduces cell viability, induces apoptosis, and promotes cell cycle arrest. FXR inhibits cervical cancer by upregulating SHP, MDM2, and p53.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Trevor Teafatiller, Oasis Perez, Masashi Kitazawa, Anshu Agrawal, Veedamali S. Subramanian
Summary: The study reveals the important role of Nedd4-1 and the proteasomal degradation pathway in regulating the functional expression of hSVCT2 in neuronal cells.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Kester Mo Henningsen, Valentina Manzini, Anna Magerhans, Sabrina Gerber, Matthias Dobbelstein
Summary: MDM2 can remove p53 from promoters by rapidly terminating its interactions with chromatin in a ubiquitin-dependent manner, in addition to its antagonism through covering the transactivation domain and destabilization.
Article
Cell Biology
Yunshan Liu, Beibei Cao, Liqiao Hu, Jingjing Ye, Wei Tian, Xiaojing He
Summary: This study elucidated the molecular link between MAGE-C2 and two major E3 systems, MDM2 and TRIM28, in p53 ubiquitination. MAGE-C2 inhibits MDM2 activity on p53 ubiquitination through direct interaction, while TRIM28 acts as a binding partner of MAGE-C2 and competes for MDM2 interaction, thereby promoting p53 ubiquitination. MAGE-C2 functions as a potential inhibitor of MDM2, and TRIM28 is a vital regulator for MAGE-C2 function in p53 protein level and cell proliferation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Miao Yan, Xin Li, Jinbao Gu, Guojun Gao, Ziyu Wu, Peng Xue
Summary: In this study, it was found that yuanhuacine can inhibit the proliferation and migration of prostate cancer cells, and induce apoptosis. The study also found that yuanhuacine suppresses tumor growth by inhibiting the MDM2/p53 signaling pathway.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xiaoliang Liu, Hebo Zhang, Bijun Zhang, Jianqiao Tu, Xiaoming Li, Yanyan Zhao
Summary: The study showed that Nedd4-2 haploinsufficiency can increase susceptibility to seizures in mice, and impaired ubiquitination of the Kir4.1 channel may be related to this.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Emilia Barrio, Rebeca Vecino, Irene Sanchez-Moran, Cristina Rodriguez, Alberto Suarez-Pindado, Juan P. Bolanos, Angeles Almeida, Maria Delgado-Esteban
Summary: The study identified that ischemic preconditioning induces activation of the PI3K/AKT signaling pathway, promoting neuronal tolerance by controlling the MDM2-p53 interaction. These findings offer a novel mechanistic pathway for IPC-induced neuroprotection, suggesting that AKT could be a potential therapeutic target against ischemic injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Rati Lama, Chao Xu, Samuel L. Galster, Javier Querol-Garcia, Scott Portwood, Cory K. Mavis, Federico M. Ruiz, Diana Martin, Jin Wu, Marianna C. Giorgi, Jill Bargonetti, Eunice S. Wang, Francisco J. Hernandez-Ilizaliturri, Gerald B. Koudelka, Sherry R. Chemler, Ines G. Munoz, Xinjiang Wang
Summary: This study identifies MMRi62 as a novel MDM2-MDM4-targeting agent that can induce apoptosis in leukemia cells, including those with non-functional p53.
FRONTIERS IN ONCOLOGY
(2022)
Article
Gastroenterology & Hepatology
Kayte A. Jenkin, Yiran Han, Songbai Lin, Peijian He, C. Chris Yun
Summary: This study investigates the role of human Na+/H+ exchanger NHE3 (hNHE3) in diarrhea and its interaction with the E3 ubiquitin ligase Nedd4-2. The findings suggest that the unique properties of hNHE3 contribute to the severity of diarrhea in humans. Additionally, protein kinase A (PKA) was found to regulate the activity of hNHE3 through its interaction with Nedd4-2. These findings highlight the importance of hNHE3 in human diarrhea.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Christophe Le Clorennec, Karen Lee, Yuchen Huo, Peter E. Zage
Summary: USP7 inhibition is a promising therapeutic strategy for high-risk and relapsed neuroblastoma (NB) in children. Inhibiting USP7 activates the p53 pathway, induces apoptosis in NB cells, and reduces N-myc protein levels. The combination of USP7 and MDM2 inhibition shows enhanced efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Timothy J. Humpton, Koji Nomura, Julia Weber, Helge M. Magnussen, Andreas K. Hock, Colin Nixon, Sandeep Dhayade, David Stevenson, Danny T. Huang, Douglas Strathdee, Karen Blyth, Karen H. Vousden
Summary: The p53 tumor suppressor protein, which activates proliferative arrest and cell death, is regulated by MDM2 protein in normal cells. Blocking the interaction between MDM2 protein and E2/ubiquitin complex to enhance p53 response to DNA damage suggests a promising avenue for therapeutic development.
GENES & DEVELOPMENT
(2021)
Article
Multidisciplinary Sciences
Jing Zhao, Alan Blayney, Xiaorong Liu, Lauren Gandy, Weihua Jin, Lufeng Yan, Jeung-Hoi Ha, Ashley J. Canning, Michael Connelly, Chao Yang, Xinyue Liu, Yuanyuan Xiao, Michael S. Cosgrove, Sozanne R. Solmaz, Yingkai Zhang, David Ban, Jianhan Chen, Stewart N. Loh, Chunyu Wang
Summary: Epigallocatechin gallate (EGCG) in green tea induces apoptosis in cancerous cells through a direct interaction with the tumor suppressor p53, inhibiting p53 ubiquitination by its regulatory E3 ligase MDM2 and stabilizing p53 for anti-tumor activity.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Ke Xu, Yanhao Chu, Qin Liu, Wenguo Fan, Hongwen He, Fang Huang
Summary: This article focuses on the regulatory role of the NEDD4 subfamily in osteogenesis, providing detailed insights into its specific roles in downstream substrates and upstream regulatory mechanisms. Additionally, an overview is provided on the involvement of E3 ligases and deubiquitinases in the development, repair, and regeneration of teeth, another mineralized tissue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Murali Munisamy, Nayonika Mukherjee, Levin Thomas, Amy Trinh Pham, Arash Shakeri, Yusheng Zhao, Jill Kolesar, Praveen P. N. Rao, Vivek M. Rangnekar, Mahadev Rao
Summary: Ubiquitination is crucial in regulating p53 stability and function in cancer, particularly through the p53-MDM2-MDMX pathway. Targeting the ubiquitination pathway shows promise as a strategy for precision therapy in cancer treatment.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Neurosciences
Kathryn A. Jewett, Ping Taishi, Parijat Sengupta, Sandip Roy, Christopher J. Davis, James M. Krueger
EUROPEAN JOURNAL OF NEUROSCIENCE
(2015)
Article
Neurosciences
Kathryn A. Jewett, Catherine A. Christian, Jonathan T. Bacos, Kwan Young Lee, Jiuhe Zhu, Nien-Pei Tsai
Article
Clinical Neurology
James M. Clinton, Christopher J. Davis, Mark R. Zielinski, Kathryn A. Jewett, James M. Krueger
JOURNAL OF CLINICAL SLEEP MEDICINE
(2011)
Article
Clinical Neurology
Christopher J. Davis, James M. Clinton, Kathryn A. Jewett, Mark R. Zielinski, James M. Krueger
JOURNAL OF CLINICAL SLEEP MEDICINE
(2011)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)