ArticleNature cell biology2009
An inducible autoregulatory loop between HIPK2 and Siah2 at the apex of the hypoxic response.
Article in Nature cell biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
74 citing papers in PubMed, 137 citations in OpenAlex.
- SIAH2-EPHB6 axis enhances filopodia formation in hepatocellular carcinoma cells by regulating RHOF.Cell & bioscience · 2026Article
- Siah2 is a lipid-mediated metabolic sensor in adipose tissue macrophage.Journal of lipid research · 2026Article
- SIAH3 is frequently epigenetically silenced in cancer and regulates mitochondrial metabolism.International journal of cancer · 2025Article
- Virtual Screening, Molecular Dynamics, and Mechanism Study of Homeodomain-Interacting Protein Kinase 2 Inhibitor in Renal Fibroblasts.Pharmaceuticals (Basel, Switzerland) · 2024Article
- HIPK2 in Colon Cancer: A Potential Biomarker for Tumor Progression and Response to Therapies.International journal of molecular sciences · 2024Review
- The ubiquitin codes in cellular stress responses.Protein & cell · 2024Review
- Review
- HMGB1-induced activation of ER stress contributes to pulmonary artery hypertension in vitro and in vivo.Respiratory research · 2023Article
- The Sweet Side of HIPK2.Cancers · 2023Review
- HIPK2 in Angiogenesis: A Promising Biomarker in Cancer Progression and in Angiogenic Diseases.Cancers · 2023Review
- Gene expression changes implicate specific peripheral immune responses to Deep and Lobar Intracerebral Hemorrhages in humans.Brain hemorrhages · 2022Article
- Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation ineLife · 2022Article
- Article
- Exosomal miR-1260b derived from non-small cell lung cancer promotes tumor metastasis through the inhibition of HIPK2.Cell death & disease · 2021Article
- HIPK2 phosphorylates HDAC3 for NF-κB acetylation to ameliorate colitis-associated colorectal carcinoma and sepsis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Prostate cancer-associated SPOP mutations lead to genomic instability through disruption of the SPOP-HIPK2 axis.Nucleic acids research · 2021Article
- Betulinic Acid Hydroxamate is Neuroprotective and Induces Protein Phosphatase 2A-Dependent HIF-1α Stabilization and Post-transcriptional Dephosphorylation of Prolyl Hydrolase 2.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Lessons from Comparison of Hypoxia Signaling in Plants and Mammals.Plants (Basel, Switzerland) · 2021Review
- DAZAP2 acts as specifier of the p53 response to DNA damage.Nucleic acids research · 2021Article
- E3 ubiquitin ligase-mediated regulation of vertebrate ocular development; new insights into the function of SIAH enzymes.Biochemical Society transactions · 2021Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxygen deprivation (hypoxia) results in reprogrammed gene expression patterns that induce multifaceted cellular responses. Here we identify a regulated interaction between the serine/threonine kinase HIPK2 and the ubiquitin E3 ligase Siah2 as a mechanism controlling the hypoxic response. Under normoxic conditions, several mechanisms ensure HIPK2 stability: only a fraction of HIPK2 is found in association with Siah2, whereas HIPK2-mediated phosphorylation of this E3 ligase at positions 26, 28 and 68 weakens mutual binding and destabilizes its phosphorylated interaction partner. Hypoxic conditions allow a markedly increased HIPK2/Siah2 interaction and result in efficient polyubiquitylation and proteasomal degradation of the kinase. Accordingly, hypoxia-induced HIPK2 elimination is markedly reduced in Siah2-deficient cells. As HIPK2 has an important role as a negative regulator of gene expression, its elimination from promoter-associated repressor complexes allows the induction of a substantial fraction of hypoxia-induced genes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.