title: The signal peptide peptidase SppA is involved in sterol regulatory element-binding protein cleavage and hypoxia adaptation in Aspergillus nidulans.
abstract: Using forward genetics, we revealed that the signal peptide peptidase (SPP) SppA, an aspartyl protease involved in regulated intramembrane proteolysis (RIP), is essential for hypoxia adaptation in Aspergillus nidulans, as well as hypoxia-sensitive mutant alleles of a sterol regulatory element-binding protein (SREBP) srbA and the Dsc ubiquitin E3 ligase complex dscA-E. Both null and dead activity [D337A] mutants of sppA failed to grow in hypoxia, and the growth defect of ΔsppA was complemented by nuclear SrbA-N381 expression. Additionally, SppA interacted with SrbA in the endoplasmic reticulum, where SppA localized in normoxia and hypoxia. Expression of the truncated SrbA-N414 covering the SrbA sequence prior to the second transmembrane region rescued the growth of ΔdscA but not of ΔsppA in hypoxia. Unlike ΔdscA and ΔdscA;ΔsppA double mutants, in which SrbA cleavage was blocked, the molecular weight of cleaved SrbA increased in ΔsppA compared to the control strain in immunoblot analyses. Overall, our data demonstrate the sequential cleavage of SrbA by Dsc-linked proteolysis followed by SppA, proposing a new model of RIP for SREBP cleavage in fungal hypoxia adaptation. Furthermore, the function of SppA in hypoxia adaptation was consistent in Aspergillus fumigatus, suggesting the potential roles of SppA in fungal pathogenesis.
authors.affiliation: Department of Biochemistry and Center for Fungal Pathogenesis, Pai Chai University, Daejeon, 34015, Republic of Korea.
authors.forename: Chinbayar
authors.initials: C
authors.lastname: Bat-Ochir
authors.affiliation: Department of Biochemistry and Center for Fungal Pathogenesis, Pai Chai University, Daejeon, 34015, Republic of Korea.
authors.forename: Jun-Yong
authors.initials: JY
authors.lastname: Kwak
authors.affiliation: Department of Biochemistry and Center for Fungal Pathogenesis, Pai Chai University, Daejeon, 34015, Republic of Korea.
authors.forename: Sun-Ki
authors.initials: SK
authors.lastname: Koh
authors.affiliation: Department of Biochemistry and Center for Fungal Pathogenesis, Pai Chai University, Daejeon, 34015, Republic of Korea.
authors.forename: Mee-Hyang
authors.initials: MH
authors.lastname: Jeon
authors.affiliation: Department of Biochemistry and Center for Fungal Pathogenesis, Pai Chai University, Daejeon, 34015, Republic of Korea.
authors.forename: Dawoon
authors.initials: D
authors.lastname: Chung
authors.affiliation: Department of Agricultural Biotechnology and Center for Fungal Pathogenesis, Seoul National University, Seoul, 08826, Republic of Korea.
authors.forename: Yin-Won
authors.initials: YW
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Center for Fungal Pathogenesis, Pai Chai University, Daejeon, 34015, Republic of Korea.
authors.forename: Suhn-Kee
authors.initials: SK
authors.lastname: Chae
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000483:Alleles; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D001233:Aspergillus nidulans / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005816:Genetic Complementation Test; D009154:Mutation; D010100:Oxygen / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D015398:Signal Transduction; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051779:Sterol Regulatory Element Binding Proteins; D016282:Aspartic Acid Endopeptidases; C460085:signal peptide peptidase; D010100:Oxygen