ArticleMolecular and cellular biology1999
A new class of repression modules is critical for heme regulation of the yeast transcriptional activator Hap1.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 46 citations in OpenAlex.
- Regulation of heme utilization and homeostasis in Candida albicans.PLoS genetics · 2022Article
- Regulation of protein function and degradation by heme, heme responsive motifs, and CO.Critical reviews in biochemistry and molecular biology · 2022Review
- Redox Regulation of Heme Oxygenase-2 and the Transcription Factor, Rev-Erb, Through Heme Regulatory Motifs.Antioxidants & redox signaling · 2018Review
- Review
- Heme promotes transcriptional and demethylase activities of Gis1, a member of the histone demethylase JMJD2/KDM4 family.Nucleic acids research · 2018Article
- The yeast anaerobic response element AR1b regulates aerobic antifungal drug-dependent sterol gene expression.The Journal of biological chemistry · 2013Article
- Heme sensor proteins.The Journal of biological chemistry · 2013Review
- Functional annotation of hierarchical modularity.PloS one · 2012Article
- Review
- Heme controls the regulation of protein tyrosine kinases Jak2 and Src.Biochemical and biophysical research communications · 2010Article
- Regulation of the HAP1 gene involves positive actions of histone deacetylases.Biochemical and biophysical research communications · 2007Article
- The heme activator protein Hap1 represses transcription by a heme-independent mechanism in Saccharomyces cerevisiae.Genetics · 2005Article
- Clustered-charge to alanine scanning mutagenesis of the Mal63 MAL-activator C-terminal regulatory domain.Current genetics · 2003Article
- Structural environment dictates the biological significance of heme-responsive motifs and the role of Hsp90 in the activation of the heme activator protein Hap1.Molecular and cellular biology · 2003Article
- The Hsp70-Ydj1 molecular chaperone represses the activity of the heme activator protein Hap1 in the absence of heme.Molecular and cellular biology · 2001Article
- Upc2p and Ecm22p, dual regulators of sterol biosynthesis in Saccharomyces cerevisiae.Molecular and cellular biology · 2001Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Heme plays key regulatory roles in numerous molecular and cellular processes for systems that sense or use oxygen. In the yeast Saccharomyces cerevisiae, oxygen sensing and heme signaling are mediated by heme activator protein 1 (Hap1). Hap1 contains seven heme-responsive motifs (HRMs): six are clustered in the heme domain, and a seventh is near the activation domain. To determine the functional role of HRMs and to define which parts of Hap1 mediate heme regulation, we carried out a systematic analysis of Hap1 mutants with various regions deleted or mutated. Strikingly, the data show that HRM1 to -6, located in the previously designated Hap1 heme domain, have little impact on heme regulation. All seven HRMs are dispensable for Hap1 repression in the absence of heme, but HRM7 is required for Hap1 activation by heme. More importantly, we show that a novel class of repression modules-RPM1, encompassing residues 245 to 278; RPM2, encompassing residues 1061 to 1185; and RPM3, encompassing residues 203 to 244-is critical for Hap1 repression in the absence of heme. Biochemical analysis indicates that RPMs mediate Hap1 repression, at least partly, by the formation of a previously identified higher-order complex termed the high-molecular-weight complex (HMC), while HRMs mediate heme activation by permitting heme binding and the disassembly of the HMC. These findings provide significant new insights into the molecular interactions critical for Hap1 repression in the absence of heme and Hap1 activation by heme.
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