SAP1a
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SAP1A is one of a family of proteins that contains a unique DNA binding domain termed the ETS domain.
Transcription
[edit]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
[edit]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
[edit]SAP1a activation by ERK may play an important role in the transformation of extracellular stimuli into a nuclear response.[1]
References
[edit]- ^ a b c 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.
- ^ 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.
- ^ 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. Bibcode:1996PNAS...9311563S. doi:10.1073/pnas.93.21.11563. PMC 38097. PMID 8876175.
- ^ 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.