RESUMO
The Ets-related DNA-binding protein human GA-binding protein (hGABP) alpha interacts with the four ankyrin-type repeats of hGABPbeta to form an hGABP tetrameric complex that stimulates transcription through the adenovirus early 4 (E4) promoter. Using co-transfection assays, this study demonstrated that the hGABP complex mediated efficient activation of transcription from E4 promoter synergistically with activating transcription factor (ATF) 1 or cAMP response element-binding protein (CREB), but not ATF2/CRE-BP1. This synergy also partially occurred when hGABPalpha was used alone in place of the combination of hGABPalpha and hGABPbeta. hGABP activated an artificial promoter containing only ATF/CREB-binding sites under coexistence of ATF1 or CREB. Consistent with these results, physical interactions of hGABPalpha with ATF1 or CREB were observed in vitro. Functional domain analyses of the physical interactions revealed that the amino-terminal region of hGABPalpha bound to the DNA-binding domain of ATF1, which resulted in the formation of ternary complexes composed of ATF1, hGABPalpha, and hGABPbeta. In contrast to hGABPalpha, hGABPbeta did not significantly interact with ATF1 and CREB. Taken together, these results indicate that hGABP functionally interacts with selective members of the ATF/CREB family, and also suggest that synergy results from multiple interactions which mediate stabilization of large complexes within the regulatory elements of the promoter region, including DNA-binding and non-DNA-binding factors.
Assuntos
Adenoviridae/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo , Transcrição Gênica , Ativação Transcricional , Fator 1 Ativador da Transcrição , Fator 2 Ativador da Transcrição , Animais , Sequência de Bases , Sítios de Ligação , Linhagem Celular , Núcleo Celular/metabolismo , Drosophila melanogaster , Fator de Transcrição de Proteínas de Ligação GA , Células HeLa , Humanos , Cinética , Dados de Sequência Molecular , Proteínas Recombinantes de Fusão/metabolismo , TransfecçãoRESUMO
A 46-year-old man visited our clinic with the chief complaint of indolent swelling of the left scrotal contents. An elastic hard and fist-sized mass with negative transillumination was palpable in left scrotum, but testis and epididymis were not discriminated. Left high orchiectomy was performed. Tumor was 90 X 55 mm in size and the testis and epididymis at the lower pole of the tumor were intact. Histological diagnosis was leiomyoma and we diagnosed leiomyoma of the spermatic cord. To our knowledge, this is the 5th case reported in Japan.