Mlx, a new Max-like bHLHZip family member: the center stage of a novel transcription factors regulatory pathway?
The Myc proto-oncogene family members have been identified as the cellular homologs of the transforming oncogene of avian retroviruses. They encode central regulators of mammalian cell proliferation and apoptosis, and they associate with the bHLHZip protein Max to bind specific DNA sequences and regulate the expression of genes important for cell cycle progression. The other family members, Mad1, Mxi1, Mad3, Mad4 and Rox (Mnt) antagonize their activities. The Mads and Rox compete with Myc in heterodimerizing with Max and in binding to the same specific target sequences. These Mads:Max and Rox:Max dimers repress transcription through binding to the mSIN3 corepressor protein and by tethering histone deacetylase-containing complexes to the DNA. In a screen for Rox interactors we isolated Mlx, a bHLHZip protein previously identified in a screen for Mad1 interactors. In the present work we extend the known dimerization partners of Mlx by demonstrating its ability to interact with Rox. Moreover, we show that contrary to previous reports Mlx is able to homodimerize and to bind E-box sequences at low concentration levels. The possible role of Mlx in an emerging regulatory pathway and acting parallel to the Max driven network is discussed.
Telethon Institute of Genetics and Medicine, Milan, Italy.
G
G
Meroni
S
S
Cairo
G
G
Merla
S
S
Messali
R
R
Brent
A
A
Ballabio
A
A
Reymond
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D019556:COS Cells; D002461:Cell Line, Transformed; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D015870:Gene Expression; D016153:Genes, Suppressor; D006367:HeLa Cells; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011817:Rabbits; D012097:Repressor Proteins; D015398:Signal Transduction; D013347:Subcellular Fractions; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; C499330:MAX protein, human; C403128:MLX protein, human; C106465:MNT protein, human; C067850:Myc associated factor X; D009687:Nuclear Proteins; D020033:Protein Isoforms; D000090063:Proto-Oncogene Mas; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA