In vitro evidence has suggested a change in the ability of tau bearing mutations associated with fronto‐temporal dementia to promote microtubule assembly. We have used cellular assay quantitate effect both isoform differences and on physiological function tau. Whilst all variants bind microtubules, extension is reduced cells transfected 3‐relative 4‐repeat Mutations reduce P301L mutation having greater than V337M mutation. The R406W had small but, surprisingly, this was less phosphorylated...

We have shown that steroid hormones coordinately control gene transcriptional activity and splicing decisions in a promoter-dependent manner.Our hypothesis is subset of hormonally recruited coregulators involved regulation promoter also directly participate alternative RNA decisions.To gain insight into the molecular mechanisms by which could decisions, we focused our attention on recently identified coactivator, CoAA.This heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein...

Nuclear hormone receptors activate gene transcription through ligand-dependent association with coactivators. Specific LXXLL sequence motifs present in these cofactors are sufficient to mediate ligand-induced interactions. A thyroid receptor (TR)-binding protein (TRBP) was cloned by a Sos-Ras yeast two-hybrid system using TRβ1-ligand binding domain as bait. TRBP contains 2063 amino acid residues, associates TR motif, and is ubiquitously expressed variety of tissues cells. strongly...

• Since previous studies have suggested that the coupling of oxidation to phosphorylation is impaired in Alzheimer brain and fibroblasts, effects carbonyl cyanide<i>m</i>-chlorophenylhydrazone, a hydrazone known uncouple mitochondrial oxidative phosphorylation, were tested on development immunoreactivity with antibodies "Alzheimer antigens" cultured fibroblasts from cognitively intact subjects. The exposed for 10 14 days medium (DMd) modeled media favor neuronal differentiation fetal...

We previously cloned and characterized thyroid hormone receptor-binding protein (TRBP) as an LXXLL-containing general coactivator that associates with complexes through its C terminus. To identify cofactors for TRBP action, a Sos-Ras yeast two-hybrid cDNA library was screened using terminus bait. A novel isolated, activator (CoAA), specifically TRBP. Human CoAA is composed of 669 amino acids TRBP-interacting domain two highly conserved RNA recognition motifs (RRM) commonly found in...

The amplified in breast cancer-3 (AIB3, ASC-2, RAP250, PRIP, TRBP, NRC, or NcoA6) gene is characterized as a cancer-amplified transcriptional coactivator for nuclear receptors, which include the peroxisome proliferator-activated receptor gamma (PPARgamma). To assess its biological function, we deleted AIB3 mice by homologous recombination. AIB3(+/-) are developmentally normal and fertile. AIB3(-/-) embryos exhibit growth restriction lethality during 9.75-11.5 days postconception. embryonic...

Gene activation mediated by nuclear receptors is regulated in a tissue-specific manner and requires interactions between their cofactors. Here, we identified characterized coactivator, GT198, that interacts with the DNA-binding domains of receptors. GT198 was originally described as genomic transcript mapped to human breast cancer susceptibility locus 17q12-q21 unknown function. We show exhibits expression pattern which its mRNA elevated testis, spleen, thymus, pituitary cells, several cell...

The solitary ERV-9 long terminal repeat (LTR) located upstream of the HS5 site in human beta-globin locus control region exhibits prominent enhancer activity embryonic and erythroid cells. LTR contains 14 tandemly repeated subunits with recurrent CCAAT, GTGGGGA, GATA motifs. Here we showed that K562 cells these DNA motifs bound following three transcription factors: ubiquitous NF-Y hematopoietic MZF1 GATA-2. These factors their target exhibited a hierarchy DNA/protein protein/protein binding...

Alternative splicing yields functionally distinctive gene products, and their balance plays critical roles in cell differentiation development. We have previously shown that tumor-associated enhancer loss coactivator CoAA leads to its altered alternative splicing. Here we identified two intergenic variants, a zinc finger-containing CoAZ non-coding transcript ncCoAZ, between downstream corepressor RBM4. During stem/progenitor neural differentiation, found the switched trans-splicing RBM4...

Ligand-dependent interaction of nuclear receptors and coactivators is a critical step in receptor-mediated transcriptional regulation. TR-binding protein (TRBP) interacts with through single LXXLL motif. Evidence suggested that the sequences flanking motif number determine receptor selectivity. We performed mutagenesis studies at residues adjacent to TRBP identified S884 −3 position as key residue for Analysis vitro vivo interactions allowed selective ERβ, TR, RXR vs. ERα. Transient...

The human GT198 gene (gene symbol PSMC3IP) is located at chromosome 17q21, 470 kb proximal to BRCA1, a locus previously linked breast and ovarian cancer predisposition. Its protein product (also known as TBPIP Hop2) has been shown regulate steroid hormone receptor–mediated activation stimulate homologous recombination in DNA repair. Here, we screened germline mutations familial early-onset patients. We have identified 8 variants total of 212 index patients including reoccurring nonsense...

// Liyong Zhang 1 , Yan Wang Mohammad H. Rashid Min Liu 2 Kartik Angara Nahid F. Mivechi Nita J. Maihle 1, 3 Ali S. Arbab and Lan Ko 4 Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA, USA Department Molecular Cellular Biology, Baylor Medicine, Houston, TX, Biochemistry Pathology, Correspondence to: Ko, email: LKO@augusta.edu Keywords: angiogenesis, pericytes, oral cancer, glioblastoma Received: October 21, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: May...

Alternative splicing produces functionally distinct proteins participating in cellular processes including differentiation and development.CoAA is a coactivator that regulates transcription-coupled its own pre-mRNA transcript alternatively spliced.We show here the CoAA gene embryonically expressed spliced multiple tissues to three splice variants, CoAA, CoAM CoAR.During retinoic-acid-induced P19 stem cell differentiation, expression of undergoes rapid switch dominant negative variant cavity...

Alternative pre-mRNA splicing yields functionally distinct splice variants in regulating normal cell differentiation as well cancer development. The putative tumor suppressor gene GT198 (PSMC3IP), encoding a protein also known TBPIP and Hop2, has been shown to regulate steroid hormone receptor–mediated transcription stimulate homologous recombination DNA repair. Here, we have identified 6 variant transcripts generated by alternative promoter usage or splicing. Various preserve common open...

Nuclear receptors mediate gene activation through ligand-dependent interaction with coactivators. We previously cloned and characterized thyroid hormone receptor-binding protein, TRBP (NcoA6: AIB3/ASC-2/RAP250/PRIP/TRBP/NRC), as an LXXLL-containing coactivator that associates complexes its C terminus. To search for protein factors involved in action, we identified a distinct set of proteins from HeLa nuclear extract interacts the terminus TRBP. Analysis by mass spectrometric sequencing...

Coactivator activator (CoAA) has been reported to be a coactivator that regulates steroid receptor-mediated transcription and alternative RNA splicing. Herein, we show CoAA is dual-function coregulator inhibits G(1)-S transition in human kidney cells suppresses anchorage-independent growth xenograft tumor formation. Suppression occurs part by down-regulating c-myc its downstream effectors ccnd1 skp2 causing accumulation of p27/Kip1 protein. In this cellular setting, directly represses the...

Ovarian cancer is a highly lethal gynecological cancer, and its causes remain to be understood. Using recently identified tumor suppressor gene, GT198 (PSMC3IP), as unique marker, we searched for the identity of mutant cells in ovarian cancer. has germ line mutations familial early onset breast cancers recurrent somatic sporadic fallopian tube cancers. protein been shown steroid hormone receptor coregulator also crucial factor DNA repair. In this study, using marker microdissection, find...

When cultured skin fibroblasts were exposed to culture conditions designed favor the expression of neuronal antigens, cells from each 19 patients with Alzheimer's disease reacted immunocytochemically antibodies paired helical filaments, Alz-50, or both compared only a small fraction identically treated age-matched control cultures. Immunoblots confirmed presence soluble material reacting Alz-50 antibody in Alzheimer fibroblasts. Ultrastructurally, fascicles 10-nm filaments seen that...

Targeting early lesion in breast cancer is more therapeutically effective. We have previously identified an oncoprotein GT198 (PSMC3IP) human cancer. Here we investigated MMTV-PyMT mouse mammary gland tumors and found that a shared both species. Similar to even before tumor appears, cytoplasmic overexpressed stroma including pericyte stem cells, descendent adipocytes, fibroblasts, myoepithelial cells. Using recombinant protein as antigen, vaccinated mice the vaccine delayed growth reduced...