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|Title:||A conserved structural motif reveals the essential transcriptional repression function of Spen proteins and their role in developmental signaling.|
Schwabe, John W. R.
|Publisher:||Cold Spring Harbor Laboratory Press|
|Citation:||Genes and Development, 2003, 17 (15), pp.1909-1920|
|Abstract:||Spen proteins regulate the expression of key transcriptional effectors in diverse signaling pathways. They are large proteins characterized by N-terminal RNA-binding motifs and a highly conserved C-terminal SPOC domain. The specific biological role of the SPOC domain (Spen paralog and ortholog C-terminal domain), and hence, the common function of Spen proteins, has been unclear to date. The Spen protein, SHARP (SMRT/HDAC1-associated repressor protein), was identified as a component of transcriptional repression complexes in both nuclear receptor and Notch/RBP-Jκ signaling pathways. We have determined the 1.8 Å crystal structure of the SPOC domain from SHARP. This structure shows that essentially all of the conserved surface residues map to a positively charged patch. Structure-based mutational analysis indicates that this conserved region is responsible for the interaction between SHARP and the universal transcriptional corepressor SMRT/NCoR (silencing mediator for retinoid and thyroid receptors/nuclear receptor corepressor. We demonstrate that this interaction involves a highly conserved acidic motif at the C terminus of SMRT/NCoR. These findings suggest that the conserved function of the SPOC domain is to mediate interaction with SMRT/NCoR corepressors, and that Spen proteins play an essential role in the repression complex.|
|Rights:||Copyright © 2003, Cold Spring Harbor Laboratory Press. Deposited with reference to the publisher’s archiving policy available on the SHERPA/RoMEO website.|
|Appears in Collections:||Published Articles, Dept. of Biochemistry|
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