NFκB regulates p21 expression and controls DNA damage-induced leukemic differentiation.

Oncogene

Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USA.

Published: July 2018

DNA damage exposure is a major modifier of cell fate in both normal and cancer tissues. In response to DNA damage, myeloid leukemia cells activate a poorly understood terminal differentiation process. Here, we show that the NFκB pathway directly activates expression of the proliferation inhibitor p21 in response to DNA damage in myeloid leukemia cells. In order to understand the role of this unexpected regulatory event, we ablated the NFκB binding site we identified in the p21 promoter, using CRISPR/Cas9-mediated genome editing. We found that NFκB-mediated p21 activation controls DNA damage-induced myeloid differentiation. Our results uncover a p53-independent pathway for p21 activation involved in controlling hematopoietic cell fate.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-018-0219-yDOI Listing

Publication Analysis

Top Keywords

dna damage
12
controls dna
8
dna damage-induced
8
cell fate
8
response dna
8
damage myeloid
8
myeloid leukemia
8
leukemia cells
8
p21 activation
8
p21
5

Similar Publications

Chemotherapy resistance has long stood in the way of therapeutic advancement for lung cancer patients, the malignant tumor with the highest incidence and fatality rate in the world. Patients with lung adenocarcinoma (LUAD) now have a dismal prognosis due to the development of cisplatin (DDP) resistance, forcing them to use more costly second-line therapies. Therefore, overcoming resistance and enhancing patient outcomes can be achieved by comprehending the regulatory mechanisms of DDP resistance in LUAD.

View Article and Find Full Text PDF

Inadvertent exposure to aristolochic acids (AAs) is causing chronic renal disease worldwide, with aristolochic acid I (AA-I) identified as the primary toxic agent. This study employed chemical methods to investigate the mechanisms underlying the nephrotoxicity and carcinogenicity of AA-I. Aristolochic acid II (AA-II), which has a structure similar to that of AA-I, was investigated with the same methods for comparison.

View Article and Find Full Text PDF

Targeting CHEK1: Ginsenosides-Rh2 and Cu2O@G-Rh2 nanoparticles in thyroid cancer.

Cell Biol Toxicol

January 2025

Department of Radiology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning Province, China.

Thyroid cancer (THCA) is an increasingly common malignant tumor of the endocrine system, with its incidence rising steadily in recent years. For patients who experience recurrence or metastasis, treatment options are relatively limited, and the prognosis is poor. Therefore, exploring new therapeutic strategies has become particularly urgent.

View Article and Find Full Text PDF

Disproportion between reactive oxygen species (ROS) production and the body's antioxidant system can cause oxidative stress, which is considered a common denominator in various pathological conditions, including cardiovascular diseases, aging, and cognitive disorders. The generation of free radicals, which occurs through partial reduction of oxygen, can quickly overwhelm the endogenous antioxidant system capacity of the cell. This causes lipid, protein, DNA and RNA damage, inflammation, and overall cell degeneration, which can be mitigated by various antioxidants.

View Article and Find Full Text PDF

Bioeffects of Nanoplastics: DNA Damage and Mechanism.

Nano Lett

January 2025

Department of Life Sciences, Faculty of Science and Technology, Beijing Normal University- Hong Kong Baptist University United International College, No. 2000 Jintong Road, Zhuhai, Guangdong 519087, China.

Nanoplastics, as emerging contaminants, have been causing great panic, potentially affecting human health in recent years. Some studies have indicated that nanoplastics may induce severe toxicity. However, the mechanisms underlying this potential toxicity are insufficiently understood.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!