SAP1a

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]

References

  1. ↑ 1.0 1.1 1.2 Janknecht R, Ernst WH, Nordheim A (March 1995). "SAP1a is a nuclear target of signaling cascades involving ERKs". Oncogene 10 (6): 1209–16. PMID 7700646.
  2. ↑ Fernández-Alvarez A, Soledad Alvarez M, Cucarella C, Casado M (April 2010). "Characterization of the human insulin-induced gene 2 (INSIG2) promoter: the role of Ets-binding motifs". J. Biol. Chem. 285 (16): 11765–74. doi:10.1074/jbc.M109.067447. PMC 2852912. PMID 20145255.
  3. ↑ Strahl T, Gille H, Shaw PE (October 1996). "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. doi:10.1073/pnas.93.21.11563. PMC 38097. PMID 8876175.
  4. ↑ Watson DK, Robinson L, Hodge DR, Kola I, Papas TS, Seth A (January 1997). "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. doi:10.1038/sj.onc.1200839. PMID 9010223.