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
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.{{cite journal |author1=Janknecht R |author2=Ernst WH |author3=Nordheim A | title = SAP1a is a nuclear target of signaling cascades involving ERKs | journal = Oncogene | volume = 10 | issue = 6 | pages = 1209–16 |date=March 1995 | pmid = 7700646 }}
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.
Insulin activated the human INSIG2 promoter in a process mediated by phosphorylated SAP1a.{{cite journal |author1=Fernández-Alvarez A |author2=Soledad Alvarez M |author3=Cucarella C |author4=Casado M | title = Characterization of the human insulin-induced gene 2 (INSIG2) promoter: the role of Ets-binding motifs | journal = J. Biol. Chem. | volume = 285 | issue = 16 | pages = 11765–74 |date=April 2010 | pmid = 20145255 | pmc = 2852912 | doi = 10.1074/jbc.M109.067447 |doi-access=free }}
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.{{cite journal |author1=Strahl T |author2=Gille H |author3=Shaw PE | title = Selective response of ternary complex factor Sap1a to different mitogen-activated protein kinase subgroups | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 21 | pages = 11563–8 |date=October 1996 | pmid = 8876175 | pmc = 38097 | doi = 10.1073/pnas.93.21.11563 |bibcode=1996PNAS...9311563S |doi-access=free }}
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.{{cite journal |author1=Watson DK |author2=Robinson L |author3=Hodge DR |author4=Kola I |author5=Papas TS |author6=Seth A | title = 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 | journal = Oncogene | volume = 14 | issue = 2 | pages = 213–21 |date=January 1997 | pmid = 9010223 | doi = 10.1038/sj.onc.1200839 |doi-access=free }}
Clinical significance
References
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