Transcriptional activation domains of elk-1, delta elk-1 and SAP-1 proteins

Oncogene. 1993 Dec;8(12):3459-64.

Abstract

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.

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / physiology
  • Cell Line
  • Chloramphenicol O-Acetyltransferase / analysis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Fungal Proteins / physiology
  • Phosphorylation
  • Proto-Oncogene Proteins*
  • Quail
  • Retroviridae Proteins, Oncogenic / genetics*
  • Retroviridae Proteins, Oncogenic / metabolism
  • Retroviridae Proteins, Oncogenic / physiology
  • Transcription Factors / physiology
  • Transcription, Genetic / genetics*
  • ets-Domain Protein Elk-1
  • ets-Domain Protein Elk-4

Substances

  • DNA-Binding Proteins
  • Fungal Proteins
  • Proto-Oncogene Proteins
  • Retroviridae Proteins, Oncogenic
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • ets-Domain Protein Elk-4
  • Chloramphenicol O-Acetyltransferase
  • Calcium-Calmodulin-Dependent Protein Kinases