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Updated: Aug 11, 2026

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
Interaction of the BMPR-IA tumor suppressor with a developmentally relevant splicing factor
Tagvor G Nishanian1, Todd Waldman
1Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC 20057, USA.
Abstract:
Inactivation of bone morphogenetic protein signaling via mutation of the BMPR-IA TGF-beta superfamily type I receptor causes familial juvenile polyposis, an inherited gastrointestinal cancer predisposition syndrome. In an effort to provide new insight into the mechanism(s) of BMP-mediated tumor suppression, we employed a yeast two-hybrid screen to identify novel proteins that interact with the intracellular domain of BMPR-IA. 30/31 interacting clones encoded SAP49, a splicing factor that has been shown to be required for normal development in Caenorhabditis elegans. The remaining interacting clone was FKBP12.6, a known TGF-beta type I receptor interactor. The interaction between BMPR-IA and SAP49 was confirmed via coimmunoprecipitation in human cells. Mutational analysis demonstrated that the GS domain of the receptor and the conserved proline-rich domain of SAP49 were required for the interaction. Co-localization studies suggested that the interaction may occur at the inner leaflet of the nuclear membrane. These data suggest that BMPR-IA may interact with and modulate the activity of a developmentally relevant splicing factor.
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