ABSTRACT
Numerous
transcription factors recruit C-terminal binding protein (CtBP)
corepressors. We show that the large zinc finger protein ZNF217
contacts CtBP. ZNF217 is encoded by an oncogene frequently amplified in
tumors. ZNF217 contains a typical Pro-X-Asp-Leu-Ser (PXDLS) motif that
binds in CtBP's PXDLS-binding cleft. However, ZNF217 also contains a
second motif, Arg-Arg-Thr (RRT), that binds a separate surface on CtBP.
The crystal structure of CtBP bound to an RRTGAPPAL peptide shows that
it contacts a surface crevice distinct from the PXDLS binding cleft.
Interestingly, both PXDLS and RRT motifs are also found in other zinc
finger proteins, such as RIZ. Finally, we show that ZNF217 represses
several promoters, including one from a known CtBP target gene, and
mutations preventing ZNF217's contact with CtBP reduce repression.
These results identify a new CtBP interaction motif and establish
ZNF217 as a transcriptional repressor protein that functions, at least
in part, by associating with
CtBP.