title: The F box protein partner of paired regulates stability of Drosophila centromeric histone H3, CenH3(CID).
abstract: Centromere identity and function is determined by the specific localization of CenH3 (reviewed in [1-7]). Several mechanisms regulate centromeric CenH3 localization, including proteasome-mediated degradation that, both in budding yeast and Drosophila, regulates CenH3 levels and prevents promiscuous misincorporation throughout chromatin [8, 9]. CenH3(CENP-A) proteolysis has also been reported in senescent human cells [10] or upon infection with herpes simplex virus 1 [11]. Little is known, however, about the actual mechanisms that regulate CenH3 proteolysis. Recent work in budding yeast identified Psh1 as an E3-ubiquitin ligase that mediates degradation of CenH3(Cse4p) [12, 13], but E3-ligases regulating CenH3 stability in metazoans are unknown. Here, we report that the F box protein partner of paired (Ppa), which is a variable subunit of the main E3-ligase SCF [14-17], mediates CenH3(CID) stability in Drosophila. Our results show that Ppa depletion results in increased CenH3(CID) levels. Ppa physically interacts with CenH3(CID) through the CATD(CID) that, in the fly, mediates Ppa-dependent CenH3(CID) stability. Altogether, these results strongly suggest that, in Drosophila, SCF(Ppa) regulates CenH3(CID) proteolysis. Interestingly, most known SCF complexes are inactive when, at mitosis, de novo CenH3(CID) deposition takes place at centromeres, suggesting that, in Drosophila, CenH3(CID) deposition and proteolysis are synchronized events.
authors.affiliation: Institute of Molecular Biology of Barcelona, CSIC, Barcelona, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Moreno-Moreno
authors.forename: Sònia
authors.initials: S
authors.lastname: Medina-Giró
authors.forename: Mònica
authors.initials: M
authors.lastname: Torras-Llort
authors.forename: Fernando
authors.initials: F
authors.lastname: Azorín
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002403:Cathepsins / Q000378:metabolism; D002503:Centromere / Q000737:chemistry*; D002843:Chromatin / Q000737:chemistry; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008938:Mitosis; D059748:Proteolysis
chemical_list: D002352:Carrier Proteins; D002843:Chromatin; D029721:Drosophila Proteins; D006657:Histones; C419987:Ppa protein, Drosophila; D002403:Cathepsins; D010450:Endopeptidases; C514943:Prosbeta2 protein, Drosophila; C514944:Prosbeta6 protein, Drosophila