Nuclear redirection of a cytoplasmic helix-loop-helix protein via heterodimerization with a nuclear localizing partner.

The DNA-binding basic domain of helix-loop-helix transcriptional (HLH) factors in several instances also serves as a nuclear localization signal (NLS). Interestingly, some members of the HLH family of proteins lack a basic domain or any other recognizable NLS and yet still display efficient nuclear localization. To study this apparent paradox, we used the hematopoietic HLH protein SCL/tal as a model. Deletion of the basic domain converted SCL/tal from nuclear to a cytoplasmic protein. However, the basic domain deficient SCL/tal protein could be redirected to the nucleus by coexpression of E2-5, an SCL/tal-binding HLH protein with an intact basic domain. These results indicate that heterodimerization of HLH proteins may take place in the cytoplasm prior to nuclear localization and that nuclear localization for HLH complexes is a dominant process requiring only a single NLS per complex.