A TATA binding protein-associated factor functions as a coactivator for thyroid hormone receptors.

Transcriptional regulation by thyroid hormone receptors (TRs) requires the TR to interact with various proteins. The TATA binding protein-associated factors (TAFs) are cofactors for several transcription factors and, therefore, are candidate cofactors for the TR. To determine whether one or more of the TAFs are cofactors for TRs, direct protein interactions between human TR beta and several Drosophila TAFs were quantitated in vitro. The human (h) TR beta bound specifically to dTAFII110 and weakly to dTAFII60, but did not bind to dTAFII30 alpha, dTAFII30 beta, dTAFII40, dTAFII80, or dTAFII150. The dTAFII110:hTR beta interaction required the carboxyl-terminals of both proteins. The dTAFII110 also interacted with the hTR alpha 1 carboxyl-terminus in a yeast two-hybrid system. Thyroid hormone destabilized the dTAFII110:TR interaction in vitro, but had no effect on the interaction in the two-hybrid system. The dTAFII110 did not bind to human retinoid X receptor alpha in vitro, indicating that this TAF interacts differentially with nuclear receptors. The transcriptional function of hTR beta was enhanced by dTAFII110 in transfection assays, indicating that this TAF can function in the thyroid hormone signalling pathway. Thus, TAFII110 functions as a cofactor for TRs, and the interactions between specific TAFs and nuclear receptors may provide another level of selectivity for transcriptional responses to hormones.

Pmp27 promotes peroxisomal proliferation.

Peroxisomes perform many essential functions in eukaryotic cells. The weight of evidence indicates that these organelles divide by budding from preexisting peroxisomes. This process is not understood at the molecular level. Peroxisomal proliferation can be induced in Saccharomyces cerevisiae by oleate. This growth substrate is metabolized by peroxisomal enzymes. We have identified a protein, Pmp27, that promotes peroxisomal proliferation. This protein, previously termed Pmp24, was purified from peroxisomal membranes, and the corresponding gene, PMP27, was isolated and sequenced. Pmp27 shares sequence similarity with the Pmp30 family in Candida boidinii. Pmp27 is a hydrophobic peroxisomal membrane protein but it can be extracted by high pH, suggesting that it does not fully span the bilayer. Its expression is regulated by oleate. The function of Pmp27 was probed by observing the phenotype of strains in which the protein was eliminated by gene disruption or overproduced by expression from a multicopy plasmid. The strain containing the disruption (3B) was able to grow on all carbon sources tested, including oleate, although growth on oleate, glycerol, and acetate was slower than wild type. Strain 3B contained peroxisomes with all of the enzymes of beta-oxidation. However, in addition to the presence of a few modestly sized peroxisomes seen in a typical thin section of a cell growing on oleate-containing medium, cells of strain 3B also contained one or two very large peroxisomes. In contrast, cells in a strain in which Pmp27 was overexpressed contained an increased number of normal-sized peroxisomes. We suggest that Pmp27 promotes peroxisomal proliferation by participating in peroxisomal elongation or fission.