The interferon- and differentiation-inducible p202a protein inhibits the transcriptional activity of c-Myc by blocking its association with Max.
p202a is a murine protein that is induced during the fusion of myoblasts to myotubes and can also be induced by interferon. Even 2-3-fold overexpression of p202a in cells retards proliferation. p202a was shown to modulate transcription by binding, and inhibiting the activity of several transcription factors including c-Fos, c-Jun, AP-2, E2F1, E2F4, NF-kappaB, MyoD, and myogenin. Here we report that p202a also bound the c-Myc protein in vitro and in vivo; the C-terminal p202a b segment bound the C-terminal basic region helix-loop-helix-leucine zipper (bHLHLZ) region of c-Myc. The transfection of a p202a expression plasmid inhibited the c-Myc-dependent expression of reporter plasmids in transient assays; moreover, overexpression of p202a in stable cell lines decreased the endogenous levels of mRNAs whose expression is driven by c-Myc. These effects of p202a are consistent with our finding that the binding of p202a to c-Myc inhibited the binding of c-Myc to Max in vitro and in vivo. p202a also inhibited the c-Myc-induced anchorage-independent growth and apoptosis of Rat-1 cells. The inhibition of c-Myc-dependent transcription, proliferation, and apoptosis by p202a is in line with the involvement of p202a in differentiation.
Wang
H
H
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
Liu
C
C
Lu
Y
Y
Chatterjee
G
G
Ma
X Y
XY
Eisenman
R N
RN
Lengyel
P
P
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D002352:Carrier Proteins / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D015536:Down-Regulation; D006801:Humans; D007370:Interferon Type I / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D010750:Phosphoproteins / Q000502:physiology*; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic / Q000502:physiology*; D014162:Transfection; D000071857:Tumor Suppressor p53-Binding Protein 1
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C092537:Ifi202b protein, mouse; D007370:Interferon Type I; D047908:Intracellular Signaling Peptides and Proteins; C499330:MAX protein, human; C067850:Myc associated factor X; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; C498301:TP53BP1 protein, human; D014157:Transcription Factors; D000071857:Tumor Suppressor p53-Binding Protein 1; C068422:Max protein, mouse