title: Depletion of cellular iron by curcumin leads to alteration in histone acetylation and degradation of Sml1p in Saccharomyces cerevisiae.
abstract: Curcumin, a naturally occurring polyphenolic compound, is known to possess diverse pharmacological properties. There is a scarcity of literature documenting the exact mechanism by which curcumin modulates its biological effects. In the present study, we have used yeast as a model organism to dissect the mechanism underlying the action of curcumin. We found that the yeast mutants of histone proteins and chromatin modifying enzymes were sensitive to curcumin and further supplementation of iron resulted in reversal of the changes induced by curcumin. Additionally, treatment of curcumin caused the iron starvation induced expression of FET3, FRE1 genes. We also demonstrated that curcumin induces degradation of Sml1p, a ribonucleotide reductase inhibitor involved in regulating dNTPs production. The degradation of Sml1p was mediated through proteasome and vacuole dependent protein degradation pathways. Furthermore, curcumin exerts biological effect by altering global proteome profile without affecting chromatin architecture. These findings suggest that the medicinal properties of curcumin are largely contributed by its cumulative effect of iron starvation and epigenetic modifications.
authors.affiliation: Laboratory of Chromatin Biology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, India.
authors.forename: Gajendra Kumar
authors.initials: GK
authors.lastname: Azad
authors.forename: Vikash
authors.initials: V
authors.lastname: Singh
authors.forename: Upendarrao
authors.initials: U
authors.lastname: Golla
authors.forename: Raghuvir S
authors.initials: RS
authors.lastname: Tomar
mesh_terms: D000107:Acetylation / Q000187:drug effects; D002570:Ceruloplasmin / Q000096:biosynthesis / Q000235:genetics; D003474:Curcumin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects; D038181:FMN Reductase / Q000096:biosynthesis / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000502:physiology; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; C115052:SML1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D007501:Iron; D002570:Ceruloplasmin; C085513:FET3 protein, S cerevisiae; D038181:FMN Reductase; C023903:ferric citrate iron reductase; D046988:Proteasome Endopeptidase Complex; D003474:Curcumin