title: A metazoan ATAC acetyltransferase subunit that regulates mitogen-activated protein kinase signaling is related to an ancient molybdopterin synthase component.
abstract: Molybdopterin (MPT) synthase is an essential enzyme involved in the synthesis of the molybdenum cofactor precursor molybdopterin. The molybdenum cofactor biosynthetic pathway is conserved from prokaryotes to Metazoa. CG10238 is the Drosophila homolog of the MoaE protein, a subunit of MPT synthase, and is found in a fusion with the mitogen-activated protein kinase (MAPK)-upstream protein kinase-binding inhibitory protein (MBIP). This fused protein inhibits the activation of c-Jun N-terminal kinase (JNK). dMoaE (CG10238) carries out this function as a subunit of the ATAC histone acetyltransferase complex. In this study, we demonstrate that Drosophila MoaE (CG10238) also interacts with Drosophila MoaD and with itself to form a complex with stoichiometry identical to the MPT synthase holoenzyme in addition to its function in ATAC. We also show that sequence determinants that regulate MAPK signaling are located within the MoaE region of dMoaE (CG10238). Analysis of other metazoan MBIPs reveals that MBIP protein sequences have an N-terminal region that appears to have been derived from the MoaE protein, although it has lost residues responsible for catalytic activity. Thus, intact and modified copies of the MoaE protein may have been conscripted to play a new, noncatalytic role in MAPK signaling in Metazoa as part of the ATAC complex.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA. tas@stowers.org
authors.forename: Tamaki
authors.initials: T
authors.lastname: Suganuma
authors.forename: Arcady
authors.initials: A
authors.lastname: Mushegian
authors.forename: Selene K
authors.initials: SK
authors.lastname: Swanson
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
mesh_terms: D000465:Algorithms; D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence; D004331:Drosophila melanogaster / Q000201:enzymology*; D004789:Enzyme Activation; D019143:Evolution, Molecular; D047468:Immunoprecipitation; D020935:MAP Kinase Signaling System; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D020539:Sequence Analysis, Protein; D013466:Sulfurtransferases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*
chemical_list: D021122:Protein Subunits; D013466:Sulfurtransferases; C085585:molybdopterin synthase