The p33ING1 protein is a regulator of cell cycle, senescence, and apoptosis. Three alternatively spliced transcripts of p33ING1 encode p47ING1a, p33ING1b, and p24ING1c. We cloned an additional ING family member, p33ING2/ING1L. Unlike p33ING1b, p33ING2 is induced by the DNA-damaging agents etoposide and neocarzinostatin. p33ING1b and p33ING2 negatively regulate cell growth and survival in a p53-dependent manner through induction of G(1)-phase cell-cycle arrest and apoptosis. p33ING2 strongly enhances the transcriptional-transactivation activity of p53. Furthermore, p33ING2 expression increases the acetylation of p53 at Lys-382. Taken together, p33ING2 is a DNA damage-inducible gene that negatively regulates cell proliferation through activation of p53 by enhancing its acetylation.
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http://dx.doi.org/10.1073/pnas.161151798 | DOI Listing |
Cell Metab
December 2024
State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China; Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China. Electronic address:
The essential amino acid methionine plays a pivotal role in one-carbon metabolism, facilitating the production of S-adenosylmethionine (SAM), a critical supplier for DNA methylation and thereby a modulator of gene expression. Here, we report that the methionine cycle is disrupted in skeletal muscle during cancer cachexia, leading to endoplasmic reticulum stress and DNA hypomethylation-induced expression of the DNA damage inducible transcript 4 (Ddit4) gene, encoding the regulated in development and DNA damage response 1 (REDD1) protein. Targeting DNA methylation by depletion or pharmacological inhibition of DNA methyltransferase 3A (DNMT3A) exacerbates cachexia, while restoring DNMT3A expression or REDD1 knockout alleviates cancer cachexia-induced skeletal muscle atrophy in mice.
View Article and Find Full Text PDFAnim Nutr
December 2024
State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
This study aimed to develop a compensatory growth model using growing beef cattle by changing dietary protein and to investigate the underlying mechanisms of compensatory protein deposition in muscle tissue. Twelve Charolais bulls were randomly assigned to one of two groups with two periods: 1) a control group (CON) fed a 13% crude protein (CP) diet for 6 weeks; 2) a treatment group (REC) fed a 7% CP diet for 4 weeks (restriction period) and fed a 13% CP diet in the following 2 weeks (re-alimentation period). Growth performance, digestibility, nitrogen balance, targeted metabolomics of amino acids (AA) in plasma, and transcriptional profiling in muscle tissue were analyzed.
View Article and Find Full Text PDFNeurosci Bull
November 2024
Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, 430056, China.
Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice.
View Article and Find Full Text PDFBiol Direct
November 2024
Department of Thyroid and Hernia Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510080, China.
Background: RNA methylation, an important reversible post-transcriptional modification in eukaryotes, has emerged as a prevalent epigenetic alteration. However, the role of the m6A reader YTH domain family 2 (YTHDF2) has not been reported in anaplastic thyroid cancer (ATC) and its biological mechanism is unclear.
Methods: The relationship between YTHDF2 expression and ATC was determined using data sets and tissue samples.
Acta Biochim Biophys Sin (Shanghai)
November 2024
Epigenetics & Translational Medicine Laboratory, School of Life Sciences, Henan University, Kaifeng 475004, China.
Esophageal squamous cell carcinoma (ESCC) is one of the most common forms of malignancy worldwide. However, there is currently a lack of effective chemotherapeutic drugs for ESCC. Ivermectin is a broad-spectrum antiparasitic drug with notable antitumor activity.
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