title: The beta-isoform of the BRCA2 and CDKN1A(p21)-interacting protein (BCCIP) stabilizes nuclear RPL23/uL14.
abstract: BRCA2 and CDKN1A(p21,CIP1)-interacting protein (BCCIP) is an evolutionary conserved protein implicated in maintenance of genome stability and cell cycle progression. Two isoforms of BCCIP with distinct C-terminal domains exist in humans. We show that mammalian BCCIPβ, but not BCCIPα, forms a ternary complex with the ribosomal protein RPL23/uL14 and the pre-60S trans-acting factor eIF6. Complex formation is dependent on an intact C-terminal domain of BCCIPβ. Depletion of BCCIPβ reduces the pool of free RPL23, and decreases eIF6 levels in nucleoli. Overexpression of BCCIPβ leads to nucleoplasmic accumulation of extra-ribosomal RPL23 and stabilizes overexpressed RPL23, suggesting that BCCIPβ functions as nuclear chaperone for RPL23.
authors.affiliation: Institute of Biochemistry, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Wyler
authors.affiliation: Institute of Biochemistry, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Franziska
authors.initials: F
authors.lastname: Wandrey
authors.affiliation: Institute of Biochemistry, ETH Zurich, CH-8093 Zurich, Switzerland; Molecular Life Sciences Ph.D. Program, CH-8057 Zurich, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Badertscher
authors.affiliation: Institute of Biochemistry, ETH Zurich, CH-8093 Zurich, Switzerland; Molecular Life Sciences Ph.D. Program, CH-8057 Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Montellese
authors.affiliation: Institute of Biochemistry, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Alper
authors.affiliation: Institute of Biochemistry, ETH Zurich, CH-8093 Zurich, Switzerland. Electronic address: ulrike.kutay@bc.biol.ethz.ch.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kutay
mesh_terms: D021581:Active Transport, Cell Nucleus; D024682:BRCA2 Protein / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D055550:Protein Stability; D012269:Ribosomal Proteins / Q000378:metabolism*
chemical_list: C415366:BCCIP protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C109284:EIF6 protein, human; D039642:Eukaryotic Initiation Factors; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012269:Ribosomal Proteins; C032493:ribosomal protein L17
keywords: BCCIP; Eukaryotic initiation factor 6 (eIF6); RPL23/uL14; Ribosomal protein; Ribosome biogenesis