| First Author | Skerjanc IS | Year | 1996 |
| Journal | J Biol Chem | Volume | 271 |
| Issue | 7 | Pages | 3555-61 |
| PubMed ID | 8631961 | Mgi Jnum | J:31425 |
| Mgi Id | MGI:78933 | Doi | 10.1074/jbc.271.7.3555 |
| Citation | Skerjanc IS, et al. (1996) A splice variant of the ITF-2 transcript encodes a transcription factor that inhibits MyoD activity. J Biol Chem 271(7):3555-61 |
| abstractText | Proteins of the basic helix-loop-helix (bHLH) family are transcription factors that bind DNA containing the E box motif (CANNTG) found in the promoters of many muscle-specific genes. ITF-2 is a bHLH protein with widespread expression that is thought to form active heterodimers with MyoD, a muscle-specific bHLH transcription factor. We have isolated cDNAs derived from two alternatively spliced forms of mouse ITF-2, termed MITF-2A and -2B. These proteins differ in their N termini. Neither MITF-2A nor -2B transactivated the cardiac alpha-actin promoter, which contains an E box, when transfected into nonmuscle cells. In fact, MITF-2B inhibited MyoD activation of the cardiac alpha-actin promoter. This inhibitory activity required the N-terminal 83 amino acids since MITF-2A showed no inhibitory activity, and a mutant MITF-2B with deletion of the N-terminal 83 amino acids failed to inhibit MyoD-mediated transcriptional activation. MyoD activity was also inhibited by Id, a HLH protein, and this inhibition was reversed by the addition of excess E12 or MITF-2A. However, the inhibition of MyoD activity by MITF-2B was not reversed with E12 or MITF-2A. While Id is thought to inhibit MyoD by binding and sequestering potential dimerization partners, MITF-2B appears to inhibit MyoD activity by forming an inactive heterodimer with MyoD. Thus, differentially spliced transcripts of mouse ITF-2 encode different proteins that appear to dimerize with MyoD and activate or repress transcription. |
