title: The p21-activated protein kinase inhibitor Skb15 and its budding yeast homologue are 60S ribosome assembly factors.
abstract: Ribosome biogenesis is driven by a large number of preribosomal factors that associate with and dissociate from the preribosomal particles along the maturation pathway. We have previously shown that budding yeast Mak11, whose homologues in other eukaryotes were described as modulating a p21-activated protein kinase function, accumulates in Rlp24-associated pre-60S complexes when their maturation is impeded in Saccharomyces cerevisiae. The functional inactivation of WD40 repeat protein Mak11 interfered with the 60S rRNA maturation, led to a cell cycle delay in G(1), and blocked green fluorescent protein-tagged Rpl25 in the nucleoli of yeast cells, indicating an early role of Mak11 in ribosome assembly. Surprisingly, Mak11 inactivation also led to a dramatic destabilization of Rlp24. The suppression of the thermosensitive phenotype of a mak11 mutant by RLP24 overexpression and a direct in vitro interaction between Rlp24 and Mak11 suggest that Mak11 acts as an Rlp24 cofactor during early steps of 60S ribosomal subunit assembly. Moreover, we found that Skb15, the Mak11 homologue in Schizosaccharomyces pombe, also associated with preribosomes and affected 60S biogenesis in fission yeast. It is thus likely that the previously observed phenotypes for MAK11 homologues in other eukaryotes are secondary to the main function of these proteins in ribosome formation.
authors.affiliation: Génétique des Interactions Macromoléculaires, Institut Pasteur, 25 rue du docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: Cosmin
authors.initials: C
authors.lastname: Saveanu
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Rousselle
authors.forename: Pascal
authors.initials: P
authors.lastname: Lenormand
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Namane
authors.forename: Alain
authors.initials: A
authors.lastname: Jacquier
authors.forename: Micheline
authors.initials: M
authors.lastname: Fromont-Racine
mesh_terms: D000595:Amino Acid Sequence; D002466:Cell Nucleolus / Q000378:metabolism; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000378:metabolism*; D017385:Sequence Homology; D054462:p21-Activated Kinases
chemical_list: C519404:Mak11 protein, S cerevisiae; D046912:Multiprotein Complexes; D050505:Mutant Proteins; D012322:RNA Precursors; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C429770:Skb15 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases