RETRACTED: hnRNP K: An HDM2 Target and Transcriptional Coactivator of p53 in Response to DNA Damage
Abstract
In response to DNA damage, mammalian cells trigger the p53-dependent transcriptional induction of factors that regulate DNA repair, cell-cycle progression, or cell survival. Through differential proteomics, we identify heterogeneous nuclear ribonucleoprotein K (hnRNP K) as being rapidly induced by DNA damage in a manner that requires the DNA-damage signaling kinases ATM or ATR. Induction of hnRNP K ensues through the inhibition of its ubiquitin-dependent proteasomal degradation mediated by the ubiquitin E3 ligase HDM2/MDM2. Strikingly, hnRNP K depletion abrogates transcriptional induction of p53 target genes and causes defects in DNA-damage-induced cell-cycle-checkpoint arrests. Furthermore, in response to DNA damage, p53 and hnRNP K are recruited to the promoters of p53-responsive genes in a mutually dependent manner. These findings establish hnRNP K as a new HDM2 target and show that, by serving as a cofactor for p53, hnRNP K plays key roles in coordinating transcriptional responses to DNA damage.
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HNRPK is a coactivator of p53 in response to DNA damage, assisting in transactivation of p21 and GADD45A.
“HNRPK is a known coactivator of p53 in response to DNA damage, assisting in the transactivation of p21 and GADD45A (22).”
From MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells (2008) · cites this paper as [22]
p53 activators JMY, TOPORS, TP53BP2, DAXX, and HNRPK can stabilize p53 protein levels by interfering with MDM2 and/or act as p53 transcriptional cofactors, assisting p53 in transactivating genes that induce apoptosis and growth arrest.
“The miR-21 targets we identified included p53 homologue, p63, p53 activators JMY, TOPORS, TP53BP2, DAXX, and HNRPK, which can stabilize p53 protein levels by interfering with MDM2 and/or act as p53 transcriptional cofactors, assisting p53 in transactivating genes that can induce apoptosis and growth arrest (21)(22)(23)(24)(25)(26).”
From MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells (2008) · cites this paper as [22]
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- Authors
- Moumen, A., Masterson, P., O'Connor, M. J., & Jackson, S. P.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Jackson, Stephen P.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 123
- Issue
- 6
- Pages
- 1065-1078
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2005893109
- Cited by
- 350
- References
- 7
- Citations by year
- 2025: 2 · 2024: 22 · 2023: 13 · 2022: 28 · 2021: 36 · 2020: 17 · 2019: 19 · 2018: 13 · 2017: 12 · 2016: 15 · 2015: 14 · 2014: 23 · 2013: 22 · 2012: 14
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Cancer Research UK
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- hnRNP K, p53, DNA damage response, transcriptional coactivator, ATM, ATR, ubiquitin-proteasome degradation, p53 target genes, promoter recruitment, retracted article
- MeSH terms
- Animals, Cell Cycle, Cell Line, DNA Damage, DNA-Binding Proteins, Humans, Leupeptins, Morpholines, Phleomycins, Promoter Regions, Genetic, Protein Binding, Pyrones, Radiation, Ionizing, Ribonucleoproteins, Transcription, Genetic, Transfection, Ultraviolet Rays, Cysteine Proteinase Inhibitors, Gene Expression, Tumor Suppressor Protein p53, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Tumor Suppressor Proteins, Ubiquitin, Heterogeneous-Nuclear Ribonucleoprotein K, RNA, Small Interfering, Cell Line, Tumor, Proteasome Endopeptidase Complex, Protein Kinase Inhibitors, Cyclin-Dependent Kinase Inhibitor p21, Proto-Oncogene Proteins c-mdm2, Proteasome Inhibitors, Ataxia Telangiectasia Mutated Proteins
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