Article
Cell Biology
Xidi Wang, Patrick Sipila, Zizhen Si, Jesusa L. Rosales, Xu Gao, Ki-Young Lee
Summary: A loss of CDK5RAP2 leads to premature cell senescence through downregulation of WIP1 and increased activity of GSK3 beta. These findings highlight the association between CDK5RAP2 loss and cell senescence as well as reduced body size.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Chiao-En Wu, Chen-Yang Huang, Chiao-Ping Chen, Yi-Ru Pan, John Wen-Cheng Chang, Jen-Shi Chen, Chun-Nan Yeh, John Lunec
Summary: The combination of HDM201 and GSK2830371 enhanced p53-dependent antiproliferative and cytotoxic effects on RBE and SK-Hep-1 cells, suggesting a novel strategy for targeting the p53 pathway in iCCA therapy.
Article
Oncology
Yanhong Xing, Xiangqing Wei, Meng-Meng Wang, Yucheng Liu, Zhongheng Sui, Xinyan Wang, Yang Zhang, Yuan-Hui Fei, Yi Jiang, Chen Lu, Peng Zhang, Rong Chen, Nan Liu, Mengmei Wu, Lin Ding, Yuqing Wang, Feng Guo, Jun-Li Cao, Jiansong Qi, Wuyang Wang
Summary: TRPM7 activation inhibits autophagy by releasing Zn2+, disrupting fusion between autophagosomes and lysosomes, ultimately arresting autophagy process. TRPM7-mediated autophagy inhibition triggers cell death and restricts tumor growth.
Article
Multidisciplinary Sciences
Francisco J. Sanchez-Rivera, Jeremy Ryan, Yadira M. Soto-Feliciano, Mary Clare Beytagh, Lucius Xuan, David M. Feldser, Michael T. Hemann, Jesse Zamudio, Nadya Dimitrova, Anthony Letai, Tyler Jacks
Summary: The level of mitochondrial apoptotic priming is a critical determinant of cell fate upon p53 reactivation, with cells having high initial priming tending to undergo apoptosis and cells with low priming tending to survive and arrest in the cell cycle. Manipulating the priming levels through BCL-2 or BCL-XL expression or inhibition can affect the outcome of p53 restoration, highlighting mitochondrial apoptotic priming as a key factor in determining cell fate. Moreover, less primed cells can be forced into apoptotic cell fate following p53 activation using p53-independent drugs that increase apoptotic priming.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Jelena Milosevic, Diana Treis, Susanne Fransson, Gabriel Gallo-Oller, Baldur Sveinbjoernsson, Nina Eissler, Keiji Tanino, Kazuyasu Sakaguchi, Tommy Martinsson, Malin Wickstroem, Per Kogner, John Inge Johnsen
Summary: Both medulloblastoma and neuroblastoma frequently exhibit segmental gain or amplification of chromosome 17q, leading to overexpression of WIP1 which is associated with poor patient prognosis. Inhibition of WIP1 activity, especially with the small molecule inhibitor SL-176, effectively suppresses the growth of these tumors in vitro and in vivo. This highlights the potential of developing clinically applicable compounds targeting WIP1 as a therapeutic strategy for various cancers.
Article
Physics, Multidisciplinary
Nan Liu, Hongli Yang, Liangui Yang
Summary: The transcription factor p53 encodes apoptosis information, with 14-3-3 sigma and Wip1 playing key roles in the p53-Mdm2 gene network. By constructing an ordinary differential equation model, it was found that these proteins regulate p53 dynamics and cell apoptosis. The study provides new insights into the mechanism of p53 dynamics and apoptosis outcome mediated by Wip1 and 14-3-3 sigma.
COMMUNICATIONS IN THEORETICAL PHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Jihyun Lee, Jongdoo Kim, Eun Mi Kim, Ukjin Kim, A-Ram Kang, Jong Kuk Park, Hong-Duck Um
Summary: In this study, it was found that p21 acts as a negative regulator of p53 stability, reducing the cellular levels of p53 protein and promoting its degradation. Additionally, p21 promotes the interaction between p53 and Wip1, and forms a trimeric complex with Wip1. The p21/p53 complex is more efficient in facilitating the binding of p53 to Wip1 and Mdm2, suggesting that p21 may be a potential target to restore p53 activity in cancer cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Xue Gong, Miao Tian, Nian Cao, Peili Yang, Zaicheng Xu, Shuo Zheng, Qiao Liao, Caiyu Chen, Cindy Zeng, Pedro A. Jose, Da-Zhi Wang, Zhao Jian, Yingbin Xiao, Ding-Sheng Jiang, Xiang Wei, Bing Zhang, Yibin Wang, Ken Chen, Gengze Wu, Chunyu Zeng
Summary: This study identified a potentially novel circRNA, circEsyt2, that regulates vascular remodeling by interacting with the protein PCBP1 to control RNA splicing, affecting proliferation and migration of vascular smooth muscle cells and neointima formation in atherosclerotic mouse models.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Pharmacology & Pharmacy
Miao Zhang, Xiaowen Bi, Shuai Liu, Yu Liu, Qiyu Wang
Summary: This study reveals for the first time that OBS triggers senescence in pituitary cells via the p53-p21-RB signaling pathway. OBS inhibits cell proliferation, induces cell cycle arrest at the G1 phase, and downregulates the expression of key proteins involved in the G1/S transition. This study provides new perspectives for understanding the potential toxicity of OBS.
Article
Oncology
Mehtap Eren, Nur Kartal, Hatice Pilevneli
Summary: This study found that in p53 mutant Jurkat cells, Wip1 gene is overexpressed, leading to sensitivity to chemotherapeutic agents, and enhancing apoptotic sensitivity by attenuating DNA damage response signaling.
Article
Biology
Alyssa C. C. Fears, Edith M. M. Walker, Nicole Chirichella, Nadia Slisarenko, Kristen M. M. Merino, Nadia Golden, Breanna Picou, Skye Spencer, Kasi E. E. Russell-Lodrigue, Lara A. A. Doyle-Meyers, Robert V. V. Blair, Brandon J. J. Beddingfield, Nicholas J. J. Maness, Chad J. J. Roy, Namita Rout
Summary: This study shows that peripheral gamma delta T cells are rapidly activated following SARS-CoV-2 infection in nonhuman primates. The expansion of V delta 1 gamma delta T cells at day 1 is significantly correlated with lung viral loads during the first week of infection. The increase in CCR6 and Granzyme B expression in V delta 1 T cells implies a role in innate-like epithelial barrier-protective and cytotoxic functions during viral clearance. Additionally, the early activation and mobilization of circulating HLA-DR(+)CXCR3(+) gamma delta T cells, along with correlations with IL-1Ra and SCF levels in bronchoalveolar lavage, suggest a novel role for V delta 1 T cells in regulating lung inflammation during aerosol SARS-CoV-2 infection.
COMMUNICATIONS BIOLOGY
(2022)
Article
Mathematical & Computational Biology
LanJiang Luo, Haihong Liu, Fang Yan
Summary: This paper investigates the dynamic characteristics of the P53 network under the influence of time delay and noise, including stability and bifurcation. Bifurcation analysis on important parameters shows that they can induce P53 oscillations within certain ranges. The system's stability and Hopf bifurcation conditions with time delays are studied, and it is found that time delay plays a key role in inducing Hopf bifurcation and regulating the system's oscillation. Additionally, noise is considered and found to promote system oscillation and induce system state switching. These findings contribute to a better understanding of the regulation mechanism of the P53-Mdm2-Wip1 network in the cell cycle.
MATHEMATICAL BIOSCIENCES AND ENGINEERING
(2023)
Article
Oncology
Victoria Chamberlain, Yvette Drew, John Lunec
Summary: Uterine Leiomyosarcoma (uLMS) is a rare and aggressive cancer with no optimal therapeutic strategy defined. This study suggests that combination treatments with MDM2 and WIP1 inhibitors may serve as a potential treatment option for p53(WT) uLMS patients.
Review
Cell Biology
Isha Nagpal, Zhi-Min Yuan
Summary: In addition to mutations in the p53 gene, compromised p53 functions due to decreased nuclear p53 protein levels or enhanced turnover are found in various human cancers, contributing to tumorigenesis. The degradation of p53 by HPV viral E6 protein or growth-promoting signaling also plays a critical role in cancer development. The association between p53 downregulation and carcinogenesis highlights the importance of basally expressed p53 in maintaining cellular homeostasis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Peiran Feng, Quanli Yang, Liang Luo, Yadong Sun, Wenkai Lv, Shuo Wan, Zerong Guan, Zhiqiang Xiao, Feng Liu, Zehua Li, Zhongjun Dong, Meixiang Yang
Summary: The study revealed the crucial role of PDK1 in Treg cell homeostasis and function, with its deficiency leading to autoimmune disorders and disruption of iron ion balance. Modulation of certain pathways could partially rescue the survival of PDK1-deficient Treg cells.