title: Proteasomal selection of multiprotein complexes recruited by LIM homeodomain transcription factors.
abstract: Complexes composed of multiple proteins regulate most cellular functions. However, our knowledge about the molecular mechanisms governing the assembly and dynamics of these complexes in cells remains limited. The in vivo activity of LIM homeodomain (LIM-HD) proteins, a class of transcription factors that regulates neuronal development, depends on the high-affinity association of their LIM domains with cofactor of LIM homeodomain proteins (LIM-HDs) (CLIM, also known as Ldb or NLI). CLIM cofactors recruit single-stranded DNA-binding protein 1 (SSDP1, also known as SSBP3), and this interaction is important for the activation of the LIM-HD/CLIM protein complex in vivo. Here, we identify a cascade of specific protein interactions that protect LIM-HD multiprotein complexes from proteasomal degradation. In this cascade, CLIM stabilizes LIM-HDs, and SSDP1 stabilizes CLIM. Furthermore, we show that stabilizing cofactors prevent binding of ubiquitin ligases to multiple protein interaction domains in LIM-HD recruited protein complexes. Together, our results indicate a combinatorial code that selects specific multiprotein complexes via proteasomal degradation in cells with broad implications for the assembly and specificity of multiprotein complexes.
authors.affiliation: Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Cenap
authors.initials: C
authors.lastname: Güngör
authors.forename: Naoko
authors.initials: N
authors.lastname: Taniguchi-Ishigaki
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Alexander
authors.initials: A
authors.lastname: Drung
authors.forename: Baris
authors.initials: B
authors.lastname: Tursun
authors.forename: Heather P
authors.initials: HP
authors.lastname: Ostendorff
authors.forename: Michael
authors.initials: M
authors.lastname: Bossenz
authors.forename: Catherina G
authors.initials: CG
authors.lastname: Becker
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.forename: Ingolf
authors.initials: I
authors.lastname: Bach
mesh_terms: D002478:Cells, Cultured; D018398:Homeodomain Proteins / Q000378:metabolism*; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
chemical_list: D018398:Homeodomain Proteins; D046912:Multiprotein Complexes; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex