INACTIVATION OF MYOD-MEDIATED EXPRESSION OF P21 IN TUMOR-CELL LINES

The basic helix-loop-helix protein MyoD induces muscle structural gene expression and cell cycle withdrawal in many nontransformed cell line s. We show that MyoD activation of transcription of the cyclin-depende nt kinase inhibitor p21 does not require synthesis of an intermediary protein. In most of the rhabdomyosarcoma and other solid tumor cell li nes that we analyzed, p21 levels were abnormally low and correlated wi th the combined inactivity of MyoD and p53, two known transcriptional activators of p21. Loss of MyoD activation of p21 transcription correl ated with the failure to arrest in G(1), and expression of p21 caused accumulation of cells in G(1), further supporting a role for p21 in My oD-induced cell cycle arrest. Finally, different tumor types have inac tivated distinct factors necessary for p21 expression, because p21 exp ression was reconstituted in hybrid cell lines. We propose that p21 in tegrates growth-inhibitory signals from independent p53 and basic heli x-loop-helix pathways, and that in the majority of tumor cell lines, b oth pathways are abrogated.