Article
Oncology
Angel C. Y. Yu, Yi-Jye Chern, Peter Zhang, Clarissa C. Pasiliao, Mahbuba Rahman, George Chang, Jianhua Ren, Isabella T. Tai
Summary: NPM1 is frequently overexpressed in colorectal cancer (CRC) and correlates with prognosis and sensitivity to chemotherapy. Inhibition of NPM1 enhances chemosensitivity of CRC cells through AKT pathway-mediated apoptosis. Suppressing NPM1 can attenuate tumor growth and restore chemosensitivity in CRC cells.
CANCER BIOLOGY & THERAPY
(2021)
Article
Multidisciplinary Sciences
Alessandro Ianni, Poonam Kumari, Shahriar Tarighi, Nicolas G. Simonet, Daniela Popescu, Stefan Guenther, Soraya Holper, Andreas Schmidt, Christian Smolka, Shijing Yue, Marcus Kruger, Claudia Fiorillo, Alejandro Vaquero, Eva Bober, Thomas Braun
Summary: Adaptation to different forms of environmental stress is crucial for maintaining cellular functions and survival, with nucleolus playing a decisive role as a signaling hub; SIRT7 is an essential component for regulating p53 stability during stress responses induced by UV irradiation; Through ATR-mediated phosphorylation, SIRT7 promotes deacetylation of NPM, affecting ubiquitination and stabilization of p53 in response to genotoxic stress.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Katerina Wolfova, Petra Otevrelova, Ales Holoubek, Barbora Brodska
Summary: RITA activates p53 and induces apoptosis in cancer cells with wild-type p53. The study found that RITA-induced changes in NPM and NCL phosphorylation were associated with apoptosis in AML patient cells but not healthy donor cells. Different AML cell lines showed heterogeneous response to RITA, and specific phosphorylation was associated with sensitivity to RITA. The NPM pT199/pS4 ratio could be a marker for RITA treatment suitability in AML cells.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
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
Multidisciplinary Sciences
Hudie Wei, Lingzhi Qu, Shuyan Dai, Yun Li, Haolan Wang, Yilu Feng, Xiaojuan Chen, Longying Jiang, Ming Guo, Jun Li, Zhuchu Chen, Lin Chen, Ye Zhang, Yongheng Chen
Summary: The structure of p53/BCL-xL complex reveals the molecular basis of their interaction and provides insight into the mechanisms of p53-mediated mitochondrial apoptosis.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Donghui Gan, Yuwen Chen, Zhengjun Wu, Liping Luo, Shimuye Kalayu Yirga, Na Zhang, Fu Ye, Haijun Chen, Jianda Hu, Yingyu Chen
Summary: DOX-PMs-NPMBP demonstrates significant anti-leukemia potential in resistant ALL cells by enhancing chemosensitivity to DOX and inducing apoptosis. This novel drug delivery system may be valuable for developing new therapeutic strategies against multidrug resistant ALL.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kexin Xie, Lei Liu, Min Wang, Xianping Li, Bingqi Wang, Sheng Yin, Wanxin Chen, Yingrui Lin, Xiaolin Zhu
Summary: This study reveals that the IMPA2/AIFM2/p53 pathway may be a molecular mechanism for paclitaxel treatment of cervical cancer and an effective strategy to enhance the sensitivity of cervical cancer cells to paclitaxel. The findings demonstrate a novel function of IMPA2 in regulating cell apoptosis and paclitaxel resistance mediated by a disturbance of AIFM2 and p53 expression, potentially making it a novel therapeutic target for cervical cancer treatment.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2023)
Review
Cell Biology
Qian Hao, Jiaxiang Chen, Hua Lu, Xiang Zhou
Summary: The tumor-suppressive activity of p53 is mainly due to its ability to induce cell death, specifically apoptosis, through various mechanisms. It transcriptionally activates pro-apoptotic genes and inhibits anti-apoptotic genes, leading to mitochondrial apoptosis. It also promotes mitochondrial apoptosis by directly interacting with BCL-2 family proteins in the mitochondria. ARTS, a pro-apoptotic protein encoded by an alternative spliced variant of the SEPT4 gene, facilitates BCL-2 and XIAP degradation, triggering apoptosis. ARTS is a new p53 target gene that enhances mitochondrial apoptosis by interacting with p53. This review discusses the mechanisms of p53-induced mitochondrial apoptosis, the role of ARTS in regulating mitochondrial cell death, and the clinical significance of ARTS in cancer and non-cancer diseases.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2023)
Review
Oncology
Massimo Bonora, Sonia Missiroli, Mariasole Perrone, Francesco Fiorica, Paolo Pinton, Carlotta Giorgi
Summary: Cancer cells display genomic instability, with mitochondria playing a key role in responding to DNA alterations and affecting cell survival and the accumulation of mutations. Mitochondrial alterations in cancer can impact cell death pathways and metabolic plasticity, contributing to the evolution of the disease. Mitochondria are involved in regulating cell death and metabolic adaptation in tumor cells, and their role in supporting genomic instability in cancer is an important aspect that warrants further exploration.
Article
Agriculture, Multidisciplinary
Keer Ma, Zhigao Wang, Xingrong Ju, Jiankang Huang, Rong He
Summary: In this study, it was found that rapeseed peptide can inhibit the proliferation of HepG2 cells and induce cell apoptosis through the mitochondrial pathway. The rapeseed peptide activates the P53 signaling pathway and inhibits MDM2, a negative regulator of P53, promoting the activation of P53.
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
(2023)
Article
Cell Biology
Chi-Fong Ko, Yi-Chieh Chang, Huan-Chieh Cho, John Yu
Summary: Puf-A is crucial for the regulation of primordial germ cell (PGC) development. Knockdown of Puf-A leads to the loss of PGCs, slowed movement of remaining PGCs, translocation of NPM1, hyperactivation of p53, and decreased expression of essential genes associated with PGC maintenance.
Article
Biochemistry & Molecular Biology
Naga Padma Lakshmi Ch, Ananthi Sivagnanam, Sebastian Raja, Sundarasamy Mahalingam
Summary: RASSF10 inhibits Cdk1/cyclin-B complex formation to induce mitotic arrest and inhibit cell proliferation, while promoting nuclear accumulation of GADD45a. Nucleophosmin (NPM) is a novel functional target of RASSF10, critical for RASSF10-mediated G2/M phase arrest. Knockdown of NPM or GADD45a impairs RASSF10-mediated cell cycle regulation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biotechnology & Applied Microbiology
Zongyi Yi, Liang Qu, Huixian Tang, Zhiheng Liu, Ying Liu, Feng Tian, Chunhui Wang, Xiaoxue Zhang, Ziqi Feng, Ying Yu, Pengfei Yuan, Zexuan Yi, Yanxia Zhao, Wensheng Wei
Summary: LEAPER 2.0 utilizes circ-arRNA to achieve higher editing efficiency and reduce off-target editing, showing successful editing effects in cell culture and a mouse model.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Noa Applebaum, Sara Chemel, Shaina Matveev, Sayanto Subrato Pal, Amitabha Sengupta, Benjamin Lucas, Margarita Vigodner
Summary: Spermatogenesis is supported by posttranslational modifications, and a crosstalk between sumoylation and phosphorylation in different cell types has been observed. Inhibition of sumoylation affects the development of spermatocytes, and specific phosphorylated targets implicated in cell cycle and/or meiosis regulation may be affected. The decrease in phosphorylation of NPM1 on Ser125, regulated by AURKB, may contribute to the inability of spermatocytes to condense chromatin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Angeles Almeida, Irene Sanchez-Moran, Cristina Rodriguez
Summary: Stroke is a major cause of death and disability in adults, with neuronal apoptosis playing a key role in ischemic brain damage and impaired recovery. The tumor suppressor protein p53 regulates cellular processes and its subcellular localization, especially in mitochondria, significantly affects neuronal apoptosis and survival after stroke.