High impact information on Ctbp1

• Finally, we found the RIBEYE homologue CtBP1 at ribbon and conventional synapses, suggesting a novel role for the CtBP/BARS family in the molecular assembly and function of central nervous system synapses [1].
• Finally, we show that mutation of the CtBP NADH binding site impairs the ability of the proteins to dimerize and to associate with BKLF [2].
• Here, we report that the nuclear import of the various CtBP proteins and splice isoforms is differentially regulated [2].
• Our results suggest a model in which the nuclear localization of CtBP proteins is influenced by the CtBP2 NLS, by binding to PXDLS motif partner proteins, and through the effect of NADH on CtBP dimerization [2].
• We suggest that the observed phenotypes reflect the large number of transcription factors whose activities are compromised in the absence of CtBP [3].

Biological context of Ctbp1

• The strong genetic interaction, as well as transcription assays with CtBP-deficient cells, indicates that CtBPs have overlapping roles in regulating gene expression [3].
• An LPAAT activity has also been proposed for CtBP/BARS (carboxy-terminal binding protein/brefeldin A-ribosylated substrate), a transcription co-repressor that is implicated in dynamin-independent endocytosis and fission of the Golgi in mitosis [4].
• Endophilin and CtBP/BARS are not acyl transferases in endocytosis or Golgi fission [4].
• CtBP1 repressed transcriptional activation induced by Glis2(1-171) [5].
• Interaction between FOG-1 and the corepressor C-terminal binding protein is dispensable for normal erythropoiesis in vivo [6].

Anatomical context of Ctbp1

• Finally, we demonstrated that calsenilin and CtBP are present in synaptic vesicles and can interact in vivo [7].
• Thus, the CtBP family proteins control cellular processes by serving as transcriptional activators and regulators of the cytoskeleton as well as transcriptional corepressors [8].
• We further demonstrate that a FOG-1 mutant unable to interact with CtBP has increased erythropoietic (but not megakaryocytic) rescue (relative to the wild type) of a FOG-1(-/-) cell line [6].

Physical interactions of Ctbp1

• In co-immunoprecipitation studies, calsenilin also interacted with CtBP1, a CtBP2 homolog [7].
• C-terminal binding protein 1 (CtBP1) was identified as one of the proteins that interact with Glis2 [5].
• FOG-1 has also been observed to interact with the corepressor molecule C-terminal binding protein (CtBP) through a peptide motif shared by all FOG family members [6].
• In turn, recruitment of PPAR-gamma-coactivator-1alpha (PGC-1alpha) and PGC-1beta to the PRDM16 complex displaces CtBP, allowing this complex to powerfully activate brown fat genes, such as PGC-1alpha itself [9].

Other interactions of Ctbp1

• Ctbp1 mutant mice are small but viable and fertile, whereas Ctbp2-null mice show defects in axial patterning and die by E10.5 due to aberrant extraembryonic development [3].
• Using a yeast two-hybrid system and co-immunoprecipitation studies, we have identified the transcriptional co-repressor C-terminal binding protein (CtBP)2 as an interactor for calsenilin and have shown that the two proteins can interact in vivo [7].
• Zinc finger protein Wiz links G9a/GLP histone methyltransferases to the co-repressor molecule CtBP [10].
• Confocal microscopic analysis demonstrated that Glis2 localized to nuclear speckles while in most cells CtBP1 was found diffusely in both cytoplasm and nucleus [5].
• Our observations suggest that the co-repressor CtBP1 and HDAC3 are part of transcription silencing complex that mediates the transcriptional repression by Glis2 [5].

Analytical, diagnostic and therapeutic context of Ctbp1

• Likewise, the LPAAT activity associated with CtBP/BARS is also a co-purification artefact [4].

References