SAP1a explained

SAP1A is one of a family of proteins that contains a unique DNA binding domain termed the ETS domain.

Transcription

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.^[1]

Interactions

SAP1a has been shown to interact with the c-fos serum response element upon recruitment by the serum response factor.

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.^[1]

Insulin activated the human INSIG2 promoter in a process mediated by phosphorylated SAP1a.^[2]

Sap1a is phosphorylated efficiently by ERKs but not by SAPK/JNKs. Serum response factor-dependent ternary complex formation by Sap1a is stimulated by ERK phosphorylation but not by SAPK/JNKs. Moreover, Sap1a-mediated transcription is activated by mitogenic signals but not by cell stress.^[3]

ELK1 and SAP1a have been shown to form ternary complexes with SRF on the serum response elements (SRE) located in the c-fos promoter. ELK1, SAPla, FLI1 and EWS-FLI1 are able to form ternary complexes with SRF on EGR1 SREs. In addition, ELK1 and SAP1a can also form quaternary complexes on the Egr1 SREI.^[4]

Clinical significance

SAP1a activation by ERK may play an important role in the transformation of extracellular stimuli into a nuclear response.^[1]

Notes and References

1. Janknecht R . Ernst WH . Nordheim A . SAP1a is a nuclear target of signaling cascades involving ERKs . Oncogene . 10 . 6 . 1209–16 . March 1995 . 7700646 .
2. Fernández-Alvarez A . Soledad Alvarez M . Cucarella C . Casado M . Characterization of the human insulin-induced gene 2 (INSIG2) promoter: the role of Ets-binding motifs . J. Biol. Chem. . 285 . 16 . 11765–74 . April 2010 . 20145255 . 2852912 . 10.1074/jbc.M109.067447 . free .
3. Strahl T . Gille H . Shaw PE . Selective response of ternary complex factor Sap1a to different mitogen-activated protein kinase subgroups . Proc. Natl. Acad. Sci. U.S.A. . 93 . 21 . 11563–8 . October 1996 . 8876175 . 38097 . 10.1073/pnas.93.21.11563 . 1996PNAS...9311563S . free .
4. Watson DK . Robinson L . Hodge DR . Kola I . Papas TS . Seth A . FLI1 and EWS-FLI1 function as ternary complex factors and ELK1 and SAP1a function as ternary and quaternary complex factors on the Egr1 promoter serum response elements . Oncogene . 14 . 2 . 213–21 . January 1997 . 9010223 . 10.1038/sj.onc.1200839 . free .