PMID- 10332029 OWN - NLM STAT- MEDLINE DCOM- 19990708 LR - 20201209 IS - 0964-6906 (Print) IS - 0964-6906 (Linking) VI - 8 IP - 6 DP - 1999 Jun TI - PQBP-1, a novel polyglutamine tract-binding protein, inhibits transcription activation by Brn-2 and affects cell survival. PG - 977-87 AB - A novel gene, designated PQBP-1, which encodes a 265 residue protein that binds to the polyglutamine tract of the brain-specific transcription factor Brn-2, was identified. PQBP-1, which also interacts with the polyglutamine tract of triplet repeat disease gene products, binds with a higher affinity to an expanded polyglutamine tract. PQBP-1 has several functional domains, including hepta- and di-amino acid repeat sequences rich in polar residues essential for its interaction with the polyglutamine tract, a WWP/WW domain which binds to proline-rich motifs in other proteins, a putative nuclear localization signal sequence and a C2domain implicated in Ca2+-dependent phospholipid signaling. PQBP-1 is located in the nucleus and inhibits transcriptional activation by Brn-2. Overexpression of PQBP-1 in P19 embryonic carcinoma cells suppresses their growth rate and enhances their susceptibility to various stresses including serum deprivation, retinoic acid treatment and UV irradiation. Northern blot and in situ hybridization analyses revealed that PQBP-1 is a ubiquitous protein and is expressed primarily in neurons throughout the brain, with abundant levels in hippocampus, cerebellar cortex and olfactory bulb. These results suggest that PQBP-1 mediates important cellular functions under physiological and pathological conditions via its interaction with polyglutamine tracts. FAU - Waragai, M AU - Waragai M AD - Group of Molecular Neurobiology, Department of Neurology, Graduate School of Medicine, University of Tokyo, Japan. FAU - Lammers, C H AU - Lammers CH FAU - Takeuchi, S AU - Takeuchi S FAU - Imafuku, I AU - Imafuku I FAU - Udagawa, Y AU - Udagawa Y FAU - Kanazawa, I AU - Kanazawa I FAU - Kawabata, M AU - Kawabata M FAU - Mouradian, M M AU - Mouradian MM FAU - Okazawa, H AU - Okazawa H LA - eng SI - GENBANK/AJ242829 SI - GENBANK/AJ250406 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Hum Mol Genet JT - Human molecular genetics JID - 9208958 RN - 0 (Carrier Proteins) RN - 0 (DNA, Complementary) RN - 0 (DNA-Binding Proteins) RN - 0 (Homeodomain Proteins) RN - 0 (Nuclear Proteins) RN - 0 (POU Domain Factors) RN - 0 (PQBP1 protein, human) RN - 0 (Peptides) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factors) RN - 0 (transcription factor Brn-2) RN - 26700-71-0 (polyglutamine) RN - 9007-49-2 (DNA) SB - IM MH - Amino Acid Sequence MH - Animals MH - Binding Sites MH - Brain/metabolism MH - Carrier Proteins/genetics/metabolism/*physiology MH - Cell Nucleus/chemistry MH - Cell Survival/physiology MH - DNA/genetics/metabolism MH - DNA, Complementary/chemistry/genetics MH - DNA-Binding Proteins MH - Female MH - Gene Expression MH - Gene Expression Regulation, Neoplastic MH - Homeodomain Proteins MH - Humans MH - In Situ Hybridization MH - Male MH - Molecular Sequence Data MH - Nuclear Proteins/genetics/metabolism/*physiology MH - POU Domain Factors MH - Peptides/*metabolism MH - Protein Binding MH - RNA, Messenger/genetics/metabolism MH - Sequence Analysis, DNA MH - Tissue Distribution MH - Transcription Factors/*physiology MH - Transcriptional Activation MH - Trinucleotide Repeats/genetics MH - Tumor Cells, Cultured EDAT- 1999/05/20 00:00 MHDA- 1999/05/20 00:01 CRDT- 1999/05/20 00:00 PHST- 1999/05/20 00:00 [pubmed] PHST- 1999/05/20 00:01 [medline] PHST- 1999/05/20 00:00 [entrez] AID - ddc126 [pii] AID - 10.1093/hmg/8.6.977 [doi] PST - ppublish SO - Hum Mol Genet. 1999 Jun;8(6):977-87. doi: 10.1093/hmg/8.6.977.