Biomedical subjects

Hidesato Ogawa

Publications and source records attributed to Hidesato Ogawa.

5 recordsLinked to original sources

PubMed2005

Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600.

The human papillomavirus type 16 (HPV-16) E7 gene encodes a multifunctional oncoprotein that can subvert multiple cellular regulatory pathways. The best-known cellular targets of the HPV-16 E7 oncoprotein are the retinoblastoma tumor suppressor protein pRB and the related pocket proteins p107 and p130. However, there is ample evidence that E7 has additional cellular targets that contribute to its transforming potential. We isolated HPV-16 E7 associated cellular protein complexes by tandem affinity purification and mass spectrometry and identified the 600-kDa retinoblastoma protein associated factor, p600, as a cellular target of E7. Association of E7 with p600 is independent of the pocket proteins and is mediated through the N terminal E7 domain, which is related to conserved region 1 of the adenovirus E1A protein and importantly contributes to cellular transformation independent of pRB binding. Depletion of p600 protein levels by RNA interference substantially decreased anchorage-independent growth in HPV-positive and -negative human cancer cells. Therefore, p600 is a cellular target of E7 that regulates cellular pathways that contribute to anchorage-independent growth and cellular transformation.

Calmodulin-Binding Proteins↗

PubMed2004

Nuclear structure-associated TIF2 recruits glucocorticoid receptor and its target DNA.

Assembly of multi-protein complexes on promoter and enhancer elements is a prerequisite for onset of gene transcription. At the beginning of this process, transcription factors are thought to act as nucleating centers for complex formation through the binding of their target DNA sequences, and thereafter recruit coactivators. Here, we investigated this process of assembly by determining the distribution of the glucocorticoid receptor (GR) and its coactivator, TIF2. Both endogenously and ectopically expressed TIF2 were shown to form foci in the nucleus, and GR could be recruited to the TIF2 foci upon GR agonist but not antagonist treatment. Moreover, we show that the coactivators, p300 and PCAF, are also recruited to the TIF2 foci. The TIF2 foci could recruit GR carrying a microinjected GR responsive element. We propose that TIF2 provides a nuclear compartment that allows the assembly of multi-protein complexes required for GR-mediated gene activation.

Animals↗

PubMed2004

Small ubiquitin-like modifier 1 (SUMO-1) modification of the synergy control motif of Ad4 binding protein/steroidogenic factor 1 (Ad4BP/SF-1) regulates synergistic transcription between Ad4BP/SF-1 and Sox9.

An orphan nuclear receptor, Ad4 binding protein/steroidogenic factor 1 (Ad4BP/SF-1), is essential for the development and function of steroidogenic tissues. To examine the transcriptional regulation of Ad4BP/SF-1, two-hybrid screening was performed, and the sumoylation [conjugation of a small ubiqutin-like modifier (SUMO-1)] components Ubc9, protein inhibitor of activated STAT 1 (PIAS1), and protein inhibitor of activated STAT 3 (PIAS3) were isolated. Cultured cell and in vitro studies revealed that Ad4BP/SF-1 is sumoylated at K119 and K194. Because K194 lies within the synergy control (SC) motif defined to repress synergistic transcription from promoters containing multiple binding sites, correlation between the functions of the SC motif and sumoylation was investigated. The K194R mutant of Ad4BP/SF-1, which cannot be sumoylated, showed enhanced synergistic transcription from a promoter containing multiple Ad4/SF-1 sites, suggesting that sumoylation is necessary for repression of transcriptional synergy through the SC motif. It has been established that the Müllerian inhibiting substance gene is transcribed predominantly under the control of Ad4BP/SF-1 and, moreover, its transcription is regulated synergistically with Sox9, Gata4, and Wt1. Interestingly, it was found that all of these factors are sumoylated, and these sumoylation sites occur within SC motifs. Based on the observation that SC motif mutants of Ad4BP/SF-1 and Sox9 resulted in the enhancement of their synergistic transcription, it was concluded that the SC motif regulates synergistic transcription even between distinct types of transcription factors. Considering that both mutants cannot be sumoylated, it is likely that sumoylation is implicated in this regulation. Because it was revealed with an in vitro sumoylated Ad4BP/SF-1 that DNA binding activity and interaction with Sox9 were unaffected, sumoylation may regulate transcription through affecting selective and cooperative interaction among factors constituting transcriptional complexes.

Amino Acid Sequence↗

PubMed2003

Coordinated histone modifications mediated by a CtBP co-repressor complex.

The transcriptional co-repressor CtBP (C-terminal binding protein) is implicated in tumorigenesis because it is targeted by the adenovirus E1A protein during oncogenic transformation. Genetic studies have also identified a crucial function for CtBP in animal development. CtBP is recruited to DNA by transcription factors that contain a PXDLS motif, but the detailed molecular events after the recruitment of CtBP to DNA and the mechanism of CtBP function in tumorigenesis are largely unknown. Here we report the identification of a CtBP complex that contains the essential components for both gene targeting and coordinated histone modifications, allowing for the effective repression of genes targeted by CtBP. Inhibiting the expression of CtBP and its associated histone-modifying activities by RNA-mediated interference resulted in alterations of histone modifications at the promoter of the tumour invasion suppressor gene E-cadherin and increased promoter activity in a reporter assay. These findings identify a molecular mechanism by which CtBP mediates transcriptional repression and provide insight into CtBP participation in oncogenesis.

Alcohol Oxidoreductases↗

PubMed2002

A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells.

E2F-6 contributes to gene silencing in a manner independent of retinoblastoma protein family members. To better elucidate the molecular mechanism of repression by E2F-6, we have purified the factor from cultured cells. E2F-6 is found in a multimeric protein complex that contains Mga and Max, and thus the complex can bind not only to the E2F-binding site but also to Myc- and Brachyury-binding sites. Moreover, the complex contains chromatin modifiers such as a novel histone methyltransferase that modifies lysine 9 of histone H3, HP1gamma, and Polycomb group (PcG) proteins. The E2F-6 complex preferentially occupies target promoters in G0 cells rather than in G1 cells. These data suggest that these chromatin modifiers contribute to silencing of E2F- and Myc-responsive genes in quiescent cells.

Amino Acid Sequence↗