ArticleCell cycle (Georgetown, Tex.)2013
CDK1 stabilizes HIF-1α via direct phosphorylation of Ser668 to promote tumor growth.
Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 112 citations in OpenAlex.
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Deciphering the interplay between hypoxia, angiogenesis, and endoplasmic reticulum stress in carcinogenesis: A narrative review.World journal of experimental medicine · 2026Review
- JAK2V617F reprograms Hypoxia Inducible Factor-1 to induce a non-canonical hypoxia regulon in myeloproliferative neoplasms.Leukemia · 2026Article
- ProteoMapper: Alignment-aware identification and quantitative analysis of contextual motif-domain patterns in protein families.PloS one · 2026Article
- EGLN1 (PHD2) role in tumor microenvironment: insights for therapeutic targeting.Experimental & molecular medicine · 2025Review
- ROS-ATM-CHK2 axis stabilizes HIF-1α and promotes tumor angiogenesis in hypoxic microenvironment.Oncogene · 2025Article
- MYLIP attenuates hypoxia tolerance by inducing K27-linked polyubiquitination and subsequent proteasomal degradation of HIF-α.Communications biology · 2025Article
- Spring viremia of carp virus infection induces hypoxia response in zebrafish by stabilizing hif1α.Journal of virology · 2025Article
- The marine-derived HIF-1α inhibitor, Yardenone 2, reduces prostate cancer cell proliferation by targeting HIF-1 target genes.Cellular & molecular biology letters · 2024Article
- PDK1 promotes breast cancer progression by enhancing the stability and transcriptional activity of HIF-1α.Genes & diseases · 2024Article
- Combinatorial regulation by ERK1/2 and CK1δ protein kinases leads to HIF-1α association with microtubules and facilitates its symmetrical distribution during mitosis.Cellular and molecular life sciences : CMLS · 2024Article
- USP38 promotes deubiquitination of K11-linked polyubiquitination of HIF1α at Lys769 to enhance hypoxia signaling.The Journal of biological chemistry · 2024Article
- Targeting the SMURF2-HIF1α axis: a new frontier in cancer therapy.Frontiers in oncology · 2024Review
- Acetylation and Phosphorylation in the Regulation of Hypoxia-Inducible Factor Activities: Additional Options to Modulate Adaptations to Changes in Oxygen Levels.Life (Basel, Switzerland) · 2023Review
- A transient increase of HIF-1α during the G1 phase (G1-HIF) ensures cell survival under nutritional stress.Cell death & disease · 2023Article
- Targeting CDK1 in cancer: mechanisms and implications.NPJ precision oncology · 2023Review
- OTUB1 augments hypoxia signaling via its non-canonical ubiquitination inhibition of HIF-1α during hypoxia adaptation.Cell death & disease · 2022Article
- Vitamin D and Hypoxia: Points of Interplay in Cancer.Cancers · 2022Review
- Oxygen-independent, CDK4/CDK6-dependent degradation of hypoxia-inducible factor-1α takes cancers' breath away.Oncotarget · 2022Article
- Non-canonical approaches to targeting hypoxic tumors.American journal of cancer research · 2022Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Hypoxia-inducible factor 1 (HIF-1) is a major mediator of tumor physiology, and its activation is correlated with tumor progression, metastasis, and therapeutic resistance. HIF-1 is activated in a broad range of solid tumors due to intratumoral hypoxia or genetic alterations that enhance its expression or inhibit its degradation. As a result, decreasing HIF-1α expression represents an attractive strategy to sensitize hypoxic tumors to anticancer therapies. Here, we show that cyclin-dependent kinase 1 (CDK1) regulates the expression of HIF-1α, independent of its known regulators. Overexpression of CDK1 and/or cyclin B1 is sufficient to stabilize HIF-1α under normoxic conditions, whereas inhibition of CDK1 enhances the proteasomal degradation of HIF-1α, reducing its half-life and steady-state levels. In vitro kinase assays reveal that CDK1 directly phosphorylates HIF-1α at a previously unidentified regulatory site, Ser668. HIF-1α is stabilized under normoxic conditions during G 2/M phase via CDK1-mediated phosphorylation of Ser668. A phospho-mimetic construct of HIF-1α at Ser668 (S668E) is significantly more stable under both normoxic and hypoxic conditions, resulting in enhanced transcription of HIF-1 target genes and increased tumor cell invasion and migration. Importantly, HIF-1α (S668E) displays increased tumor angiogenesis, proliferation, and tumor growth in vivo compared with wild-type HIF-1α. Thus, we have identified a novel link between CDK1 and HIF-1α that provides a potential molecular explanation for the elevated HIF-1 activity observed in primary and metastatic tumors, independent of hypoxia, and offers a molecular rationale for the clinical translation of CDK inhibitors for use in tumors with constitutively active HIF-1.
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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.