Cellular p53 protein levels are regulated by a ubiquitination/de-ubiquitination cycle that can target the protein for proteasomal destruction. The ubiquitination reaction is catalyzed by a multitude of ligases, whereas the removal of ubiquitin chains is mediated by two deubiquitinating enzymes (DUBs), USP7 (HAUSP) and USP10. Here, we show that PHD3 hydroxylates p53 at proline 359, a residue that is in the p53-DUB binding domain. Hydroxylation of p53 upon proline 359 regulates its interaction with USP7 and USP10, and its inhibition decreases the association of p53 with USP7/USP10, increases p53 ubiquitination, and rapidly reduces p53 protein levels independently of mRNA expression. Our results show that p53 is a PHD3 substrate and that hydroxylation by PHD3 regulates p53 protein stability through modulation of ubiquitination.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6088137 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2018.06.108 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Toripalimab plus chemotherapy for metastatic muscle-invasive bladder cancer with a high tumor proportion score: a case report.
Front Immunol
January 2025
Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Background: Radical cystectomy (RC) combined with pelvic lymph node dissection (PLND) is the standard treatment for muscle-invasive bladder cancer (MIBC). For metastatic MIBC patients, platinum-based chemotherapy remains the first choice treatment. However, approximately 50% of patients with metastatic MIBC are ineligible for platinum-based adjuvant chemotherapy because of impaired renal function.
View Article and Find Full Text PDFDysregulation of mTOR signalling is a converging mechanism in lissencephaly.
Nature
January 2025
Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Cerebral cortex development in humans is a highly complex and orchestrated process that is under tight genetic regulation. Rare mutations that alter gene expression or function can disrupt the structure of the cerebral cortex, resulting in a range of neurological conditions. Lissencephaly ('smooth brain') spectrum disorders comprise a group of rare, genetically heterogeneous congenital brain malformations commonly associated with epilepsy and intellectual disability.
View Article and Find Full Text PDF[Analysis of Gene Mutation and Clinical Characteristics Related to Myelodysplastic Syndrome].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
December 2024
Department of Hematology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, Anhui Province, China.
Objective: To explore the characteristics of gene mutation in patients with myelodysplastic syndrome (MDS) and its correlation with clinical features.
Methods: From January 2017 to December 2021, 172 patients with MDS in The First Affiliated Hospital of Bengbu Medical University were analyzed retrospectively. Fourteen high frequency genes related to MDS were detected, and the relationship between gene mutation and clinical characteristics of patients as well as revised International Prognostic Scoring System (IPSS-R) was analyzed.
[The Impact of -Mediated Alternative Splicing of on the Proliferation of Multiple Myeloma Cells].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
December 2024
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
Objective: To investigate the effect of different isoforms of on the proliferation of multiple myeloma (MM) cells after alternative splicing mediated by splicing factor .
Methods: RT-PCR was used to detect the expression levels of mRNA splicing isoforms regulated by . The GEO database was used to analyze the changes of isoform 1 in the progression of plasma cell disease, and survival analysis was used to evaluate the value of this gene in the prognosis of MM patients.
[The Prognostic Predictive Value of mutation Variant Allele Frequency in Diffuse Large B-Cell Lymphoma].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
December 2024
Department of Hematology, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi 830001, Xinjiang Uygur Autonomous Region, China.
Objective: To explore the effect of mutation variant allele frequency(VAF) on the prognosis of diffuse large B-cell lymphoma(DLBCL) patients.
Methods: This study included 155 patients with DLBCL who were first diagnosed in the People's Hospital of Xinjiang Uygur Autonomous Region from March 2009 to March 2022. Complete clinical data and paraffin-embedded tumor tissue samples were obtained, and DNA was extracted from tumor tissues.
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!