A novel modulator domain of Ets transcription factors.

Abstract

The ets gene family is composed of several oncogenes and codes for transcription factors. The Ets proteins have a similar sequence called the ets domain and bind to the core motif A/CGGAA. We show here that several members of the ets family have different trans-activating properties. The ets domain of Ets-1 is required for DNA binding. Adjacent to this domain there is a novel element that inhibits DNA binding. It appears to alter the structure of the DNA-binding domain before it interacts with DNA. There is a similar sequence in Ets-2 that also inhibits DNA binding. This sequence is absent in alternative splice products of h-Ets-1. PU1, the most distantly related member of the ets gene family, lacks this novel element. It has a distinct DNA-binding specificity that is determined by DNA sequences outside the core motif. These results have important implications for both the oncogenic and normal functions of ets family members.

Angiogenesis induced by hepatocyte growth factor in non-infarcted myocardium and infarcted myocardium: up-regulation of essential transcription factor for angiogenesis, ets

“…[17][18][19][20] The ets family of transcription factors has a DNA-binding domain in common that binds to a core GGA(A/T) DNA sequence. 21,22 In situ hybridization studies have shown that the proto-oncogene c-ets is expressed in endothelial cells at the beginning of blood vessel formation, under normal and pathological conditions. 23,24 Thus, previous reports suggest that the ets family may activate the transcription of genes encoding collagenase 1, stromelysine 1 and urokinase plasminogen activator, which are proteases involved in extracellular matrix degradation.…”

A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13–15, a region subject to LOH and rearrangement in human carcinoma cell lines

“…However, amino acids highly conserved amongst ETS family members (Janknecht and Nordheim, 1993) are well conserved in ELF5 (23/38). Some of these highly conserved residues, such as the three tryptophan residues in the carboxyl half of the ETS domain, have been demonstrated to be structurally critical for DNA binding of other ETS family members (Wang et al, 1992;Wasylyk et al, 1992).…”

A variant form of ETS1 induces apoptosis in human colon cancer cells

“…Both 42 kDa and 51 kDa ETS1 bind to DNA with similar a nity and dissociate at di erent rates (Fisher et al, 1994). P42-ETS1 lacks the inhibitory domain involved in the intramolecular folding (Wasylyk et al, 1992;Jonsen et al, 1996). Furthermore, phosphorylation of ETS1 has been shown to inhibit its DNA binding properties (Rabault and Ghysdael, 1995;Fisher et al, 1994).…”