An amino-terminal domain of Mxi1 mediates anti-myc oncogenic activity and interacts with a homolog of the Yeast Transcriptional Repressor SIN3

Abstract

Documented interactions among members of the Myc superfamily support a yin-yang model for the regulation of Myc-responsive genes in which transactivation-competent Myc-Max heterodimers are opposed by repressive Mxi1-Max or Mad-Max complexes. Analysis of mouse mxi1 has led to the identification of two mxi1 transcript forms possessing open reading frames that differ in their capacity to encode a short amino-terminal alpha-helical domain. The presence of this segment dramatically augments the suppressive potential of Mxi1 and allows for association with a mammalian protein that is structurally homologous to the yeast transcriptional repressor SIN3. These findings provide a mechanistic basis for the antagonistic actions of Mxi1 on Myc activity that appears to be mediated in part through the recruitment of a putative transcriptional repressor.

Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation

“…REFs were transfected with expression constructs of c-myc, H-RAS G12v , mTERT, and pBABE vector control according to Figure 5, by the calcium phosphate method as described (Schreiber-Agus et al, 1995). Plates were split 1 to 3 at 20 h after transfection and media was changed every 3 days.…”

Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein

“…Indeed SMRT and N-CoR interact strongly with unliganded receptors and are released upon ligand binding. A series of recent reports (Alland et al, 1997;Hassig et al, 1997;Heinzel et al, 1997;Kadosh and Struhl, 1997;Laherty et al, 1997;Zhang et al, 1997) have shown that SMRT/ N-CoR co-repressors are part of a multiprotein complex including the Mad co-repressors mSin3A and B (Ayer et al, 1995;Schreiber-Agus et al, 1995) and the histone deacetylases HDAC1/HD1 and HDAC2/mRPD3 (Taunton et al, 1996;Yang et al, 1996). These studies, that strengthen the major role of histone acetylation/deacetylation in transcriptional regulation, provide the basis for the existence of a common repression pathway between nuclear receptors and basic region-helix ± loop ± helix-leucine zipper (bHLH-Zip) proteins.…”

The adenovirus E1A binding protein BS69 is a corepressor of transcription through recruitment of N-CoR

“…N-CoR and its close homologue SMRT were cloned as co-repressors of the thyroidhormone and retinoic acid receptors (Chen and Evans, 1995;Horlein et al, 1995). Both N-CoR and SMRT have been shown to be components of large protein complexes that include histone deacetylase (Taunton et al, 1996; Nagy et al, 1997) and Sin3 (Ayer et al, 1995;Schreiber et al, 1995). Moreover, N-CoR is involved in Mad repression, reviewed by (Schreiber and DePinho, 1998).…”