ArticleProceedings of the National Academy of Sciences of the United States of America2012
Structural basis for homeodomain recognition by the cell-cycle regulator Geminin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- A Structure-Guided Kinase-Transcription Factor Interactome Atlas Reveals Docking Landscapes of the Kinome.bioRxiv : the preprint server for biology · 2025Article
- Pathogenic variants in the paired-related homeobox 1 gene (PRRX1) cause craniosynostosis with incomplete penetrance.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- Correlation between DNA Methylation and Cell Proliferation Identifies New Candidate Predictive Markers in Meningioma.Cancers · 2022Article
- Role of HOXA9 in solid tumors: mechanistic insights and therapeutic potential.Cancer cell international · 2022Review
- Geminin is required for Hox gene regulation to pattern the developing limb.Developmental biology · 2020Article
- Review
- SIX3 and SIX6 interact with GEMININ via C-terminal regions.Biochemistry and biophysics reports · 2019Article
- The Biophysical Society of Hong Kong (BPHK): past, present, and future.Biophysical reviews · 2019Article
- Kinase Regulation of HOX Transcription Factors.Cancers · 2019Review
- Gene regulatory networks in neural cell fate acquisition from genome-wide chromatin association of Geminin and Zic1.Scientific reports · 2016Article
- Role of Geminin in cell fate determination of hematopoietic stem cells (HSCs).International journal of hematology · 2016Review
- Review
- Geminin deletion in mouse oocytes results in impaired embryo development and reduced fertility.Molecular biology of the cell · 2016Article
- Manipulation of Cell Cycle and Chromatin Configuration by Means of Cell-Penetrating Geminin.PloS one · 2016Article
- Article
- The Geminin and Idas coiled coils preferentially form a heterodimer that inhibits Geminin function in DNA replication licensing.The Journal of biological chemistry · 2013Article
- Emerging players in the initiation of eukaryotic DNA replication.Cell division · 2012Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Homeodomain-containing transcription factors play a fundamental role in the regulation of numerous developmental and cellular processes. Their multiple regulatory functions are accomplished through context-dependent inputs of target DNA sequences and collaborating protein partners. Previous studies have well established the sequence-specific DNA binding to homeodomains; however, little is known about how protein partners regulate their functions through targeting homeodomains. Here we report the solution structure of the Hox homeodomain in complex with the cell-cycle regulator, Geminin, which inhibits Hox transcriptional activity and enrolls Hox in cell proliferative control. Side-chain carboxylates of glutamates and aspartates in the C terminus of Geminin generate an overall charge pattern resembling the DNA phosphate backbone. These residues provide electrostatic interactions with homeodomain, which combine with the van der Waals contacts to form the stereospecific complex. We further showed that the interaction with Geminin is homeodomain subclass-selective and Hox paralog-specific, which relies on the stapling role of residues R43 and M54 in helix III and the basic amino acid cluster in the N terminus. Interestingly, we found that the C-terminal residue Ser184 of Geminin could be phosphorylated by Casein kinase II, resulting in the enhanced binding to Hox and more potent inhibitory effect on Hox transcriptional activity, indicating an additional layer of regulation. This structure provides insight into the molecular mechanism underlying homeodomain-protein recognition and may serve as a paradigm for interactions between homeodomains and DNA-competitive peptide inhibitors.
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