The hematopoietic transcription factor SCL binds the p44 subunit of TFIIH.

SCL is a basic domain helix-loop-helix (bHLH) oncoprotein that is involved in T-cell acute lymphoblastic leukemia as well as in normal hematopoiesis. Although it is believed that SCL functions as a tissue-specific transcription factor, no molecular mechanism has thus far been identified for this putative function. In this report, we show that SCL interacts with p44, a subunit of the basal transcription factor TFIIH. The minimal region of SCL that interacts with p44 was mapped to a 101-amino acid sequence that includes, but is not limited to, the bHLH region; the SCL-binding site of p44 is located in the carboxyl-terminal half of p44. This interaction was confirmed by glutathione S-transferase fusion protein pull-down assays and a co-immunoprecipitation assay. As analyzed with a yeast two-hybrid system, p44 interacts specifically with SCL, but not with the other class A or B bHLH proteins tested. E2A did not compete with p44 for SCL binding, as demonstrated by an in vitro binding assay. These findings document a previously unsuspected interaction between SCL and a subunit of the basal transcription factor TFIIH, suggesting a potential means by which SCL might modulate transcription.