Transcriptional activation domains of elk-1, delta elk-1 and SAP-1 proteins.
elk-1, an ets related gene codes for a sequence specific DNA binding transcriptional activator which in association with serum response factor (SRF) forms a ternary complex at the c-fos serum response element (SRE). Recently the C-terminal region of both elk-1 and delta elk-1 proteins was shown to undergo phosphorylation by MAP kinases and function as an activator of MAP kinases. Here we show that delta elk-1 and two other elk-1 related proteins SAP-1a and SAP-1b, like elk-1, can function as transcriptional activators. In this report we have localized the transcriptional activation domain of the SAP-1 proteins (STA) to a large portion of the carboxy terminal region and have identified two autonomous transcriptional activation domains in the elk-1 protein, one at the amino (ETA-1) and the other at the carboxy terminal region (ETA-2). delta elk-1 protein contains only the ETA-2 domain indicating differential usage of activation domains as a result of alternative splicing. We can speculate that the ETA-1 domain can function in vivo independent of ETA-2, but the ETA-2 domain can function either in the absence of ETA-1 (as seen in delta elk-1) or in the presence of accessory proteins like SRF. The role of SRF in the activation of the ternary complex might be to bind to the ETA-1 domain, somehow conceal it's activation domain and in the process unmask the ETA-2 domain (for phosphorylation by MAP kinases) and activate transcription. The ETA-1 domain may be functioning as a negative regulatory transcriptional activation domain for ETA-2. These observations suggest that the elk-1 family of proteins may not only regulate fos and MAP kinases but also other elk-1 target genes that are essential for cellular growth control.
Bhattacharya
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G
Jefferson Cancer Institute, Philadelphia, PA 19107-5541.
Lee
L
L
Reddy
E S
ES
Rao
V N
VN
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins; D011784:Quail; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics*; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D011518:Proto-Oncogene Proteins; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4; D015500:Chloramphenicol O-Acetyltransferase; D017871:Calcium-Calmodulin-Dependent Protein Kinases