SAP1a is a nuclear target of signaling cascades involving ERKs

The Ets protein SAP1a has been shown to interact with the c-fos serum response element upon recruitment by the serum response factor. We demonstrate that SAP1a is a nuclear protein stimulating transcription via the c-fos serum response element, and additionally via an Ets binding site independently of the serum response factor. However, transactivation has only been observed under conditions leading to the activation of extracellular signal-regulated protein kinases (ERKs). The transcriptional activation domain of SAP1a resides within the C-terminal region, the function of which may be impeded by the N-terminus. Several potential ERK consensus sites within the C-terminal region of SAP1a can modulate its transactivation efficacy, implicating that SAP1a is a direct target of ERKs. Since ERKs are activated by a broad range of signals, SAP1a may play an important role in the transformation of extracellular stimuli into a nuclear response.