Repression mechanisms of v-ERBA and other members of the steroid receptor superfamily.
Members of the steroid receptor superfamily, like other transcription factors, can function as transcriptional inducers as well as repressors of transcription. The mechanisms by which repression is achieved seem to be specific for the factors and [table: see text] regulatory sequences involved. Many and perhaps all of the steps required for transcriptional activation can be interfered with by nuclear receptors. Binding of a receptor dimer immediately adjacent to a transcription factor leads to synergistic transactivation (Fig. 6A). Binding of the GR to a nGRE displaces a positive transcription factor but has no or weak transactivation potential because no synergizing factor is nearby (Fig. 6B). The DNA-AP1 complex may bind GR, TR, or RAR so that the transactivating functions of both partners are inhibited (Fig. 6C). These negative effects (Fig. 6B and C) inhibit transactivating factor mediated gene activation, whereas the following examples show a reduction below the activity of a minimal promoter, thus acting very likely on general factors in the transcription initiation complex. v-ERBA competes with TR or RAR for DNA binding and in this respect resembles the mechanism described in Figure 6B. Silencing activity is then conferred by the bound v-ERBA, which is able to repress the activity of a complete or of a minimal promoter (Fig. 6D). Removal of the ligands T3 or RA converts the activating T3R or RAR into a silencing conformation (Fig. 6E). Ligand-free T3R, RAR, or v-ERBA bind to a silencer sequence and synergize with other silencer modules in repression (Fig. 6F).
Renkawitz
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Genetisches Institut, Universität Giessen, Germany.
D000818:Animals; D004247:DNA / Q000378:metabolism; D005810:Multigene Family; D018774:Oncogene Proteins v-erbA; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D018774:Oncogene Proteins v-erbA; D011987:Receptors, Steroid; D012097:Repressor Proteins; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D004247:DNA