Disease relevance of TRIP11

• Fusion of the platelet-derived growth factor receptor beta to a novel gene CEV14 in acute myelogenous leukemia after clonal evolution [1].
• We now report that overexpressing GMAP-210 blocks the anterograde transport of both a soluble form of alkaline phosphatase and the hemagglutinin protein of influenza virus, an integral membrane protein, between the endoplasmic reticulum and the cis/medial (mannosidase II-positive) Golgi compartment [2].
• Trip230 is a novel coactivator of the thyroid hormone receptor that is negatively regulated by the retinoblastoma tumor-suppressor protein [3].

High impact information on TRIP11

• All our experiments suggest that GMAP-210 displays microtubule anchoring and membrane fusion activities, thus contributing to the assembly and maintenance of the Golgi ribbon around the centrosome [4].
• GMAP-210 recruits gamma-tubulin complexes to cis-Golgi membranes and is required for Golgi ribbon formation [4].
• GMAP-210 depletion by RNA interference results in extensive fragmentation of the Golgi apparatus, supporting a role for GMAP-210 in Golgi ribbon formation [4].
• Targeting of GMAP-210 or its C terminus to mitochondria induces the recruitment of gamma-tubulin to their surface and redistribution of mitochondria to a pericentrosomal location [4].
• Deletion analyses in vitro show that the COOH terminus of GMAP-210 binds to microtubules whereas the NH2 terminus binds to Golgi membranes [5].

Biological context of TRIP11

• Finally, using single-cell microinjection and RNA interference assays, we demonstrate that TRIP230 is indispensable for TCDD- and hypoxia-dependent gene transcription [6].
• On the basis of the analysis of the gmap-210 genomic sequence, we propose that the small isoform, GMAP-200, arises from alternative splicing of exon 4 of the primary transcript [7].
• Here we show that GMAP-210, a cis-Golgi microtubule binding protein, recruits gamma-tubulin-containing complexes to Golgi membranes even in conditions where microtubule polymerization is prevented and independently of Golgi apparatus localization within the cell [4].
• T3-dependent nuclear import of Trip230 does not require new protein synthesis [3].
• Thyroid hormone, T3-dependent phosphorylation and translocation of Trip230 from the Golgi complex to the nucleus [3].

Anatomical context of TRIP11

• Biochemical analysis further suggests that GMAP-210 specifically binds to microtubule ends [5].
• The protein uses two distinct regions to bind Rb and thyroid hormone receptor (TR), respectively, and thus was named Trip230 [8].

Associations of TRIP11 with chemical compounds

• Trip230 binds to Rb independently of thyroid hormone while it forms a complex with TR in a thyroid hormone-dependent manner [8].
• Furthermore, TRIP230 could be recorded at sites of activated transcription of either TCDD- or hypoxia-inducible genes in a stimulus-dependent fashion by chromatin immunoprecipitation analysis [6].

Regulatory relationships of TRIP11

• The overexpression of GMAP-210 blocks anterograde and retrograde transport between the ER and the Golgi apparatus [2].

Other interactions of TRIP11

• Overexpression of GMAP-210-encoding cDNA induced a dramatic enlargement of the Golgi apparatus and perturbations in the microtubule network [5].
• A partial cDNA for a novel gene, CEV14, includes a leucine zipper motif and putative thyroid hormone receptor interacting domain and is expressed in a wide range of tissues [1].
• During cell cycle progression, the expression level of Trip230 is constant and a significant portion is imported into the nucleus at S phase [3].

Analytical, diagnostic and therapeutic context of TRIP11

• Within an hour of treating cells with T3, Trip230 immunofluorescence transiently colocalized with TR in prominent subnuclear structures [3].

References