Inhibition of Transcriptional Regulator Yin-Yang-1 by Association with c-Myc

Abstract

Yin-Yang-1 (YY1) regulates the transcription of many genes, including the oncogenes c-fos and c-myc. Depending on the context, YY1 acts as a transcriptional repressor, a transcriptional activator, or a transcriptional initiator. The yeast two-hybrid system was used to screen a human complementary DNA (cDNA) library for proteins that associate with YY1, and a c-myc cDNA was isolated. Affinity chromatography confirmed that YY1 associates with c-Myc but not with Max. In cotransfections, c-Myc inhibits both the repressor and the activator functions of YY1, which suggests that one way c-Myc acts is by modulating the activity of YY1.

Direct association of YY-1 with c-Myc and the E-box binding protein in regulation of glycophorin gene expression

“…As a nuclear protein that interacts with YY-1 and regulates glycophorin gene in MEL cells, we are interested in c-Myc because YY-1 activity is inhibited by physical interaction with c-Myc (Shrivastava et al, 1993). c-Myc is a basic-helix ± loop ± helix-zipper (bHLHZip) nuclear oncoprotein that heterodimerizes with Max, another bHLHZip protein, to exert its functions as both a speci®c DNA binding transcriptional activator and a transforming protein by binding to the speci®c DNA sequence E-box (CACGTG) (Ho man-Liberman and Liberman, 1991; Dunn et al, 1994;Larsson et al, 1994;Marcu et al, 1992).…”

“…Recently it has been reported that YY-1 interacts physically with c-Myc in vitro and that YY-1 activity is inhibited by this interaction (Shrivastava et al, 1993). c-Myc is a nuclear oncoprotein which regulates a variety of biological processes including oncogenesis, apoptosis, DNA replication, proliferation, and differentiation (Luscher and Eisenman, 1990;Dang and Lee, 1988;Stone et al, 1987;Penn et al, 1990;Crouch et al, 1990;Hermeking and Eick, 1994), although the precise molecular mechanism remains unclear.…”

The basic region/helix – loop – helix/leucine zipper domain of Myc proto-oncoproteins: Function and regulation

“…In a yeast twohybrid screen with the transcriptional regulator YinYang-1 (YY1) as bait Myc was identi®ed as an interaction partner (Shrivastava et al, 1993). Although the region required in Myc to bind to YY1 was not mapped in detail, the ®nding that the interaction of Myc with Max and YY1 was exclusive suggested an involvement of the bHLHZip domain.…”

“…Further analysis revealed that Myc and YY1 can be coimmunoprecipitated from cells and that the amount of c-Myc in complex with YY1 correlated with the expression of c-Myc (Shrivastava et al, 1996;Zhao et al, 1998;M Austen and B LuÈ scher, unpublished results). Since c-Myc overexpression was able to interfere with the activity of YY1 both as transcriptional activator and repressor in cotransfections (Shrivastava et al, 1993), a model was proposed where increased endogenous Myc levels as a result of mitogenic stimulation or oncogenic events would compete out positive YY1-interacting proteins through direct interaction with YY1, thereby leading to its inactivation and repression of YY1 target genes (Shrivastava et al, 1996;Zhao et al, 1998). Since YY1 is a much more abundant protein than Myc, the stochiometry of this competition remains to be explained.…”

Human death effector domain-associated factor interacts with the viral apoptosis agonist Apoptin and exerts tumor-preferential cell killing

“…This reporter gives a high basal level of luciferase activity, which can be either enhanced or repressed by factors tethered to the promoter via the Gal4 DNA-binding domain. Cotransfection of the reporter plasmid with Gal4-YY1, known to repress transcription in a similar system, 21 resulted in repression of luciferase activity (Figure 3b). Likewise, DEDAF fused to the Gal4 DNA-binding domain repressed luciferase acitivity, even when as little as 2 ng of plasmid was added (Figure 3b).…”