New regulators of Wnt/beta-catenin signaling revealed by integrative molecular screening.
The identification and characterization of previously unidentified signal transduction molecules has expanded our understanding of biological systems and facilitated the development of mechanism-based therapeutics. We present a highly validated small interfering RNA (siRNA) screen that functionally annotates the human genome for modulation of the Wnt/beta-catenin signal transduction pathway. Merging these functional data with an extensive Wnt/beta-catenin protein interaction network produces an integrated physical and functional map of the pathway. The power of this approach is illustrated by the positioning of siRNA screen hits into discrete physical complexes of proteins. Similarly, this approach allows one to filter discoveries made through protein-protein interaction screens for functional contribution to the phenotype of interest. Using this methodology, we characterized AGGF1 as a nuclear chromatin-associated protein that participates in beta-catenin-mediated transcription in human colon cancer cells.
Major
Michael B
MB
Howard Hughes Medical Institute, Department of Pharmacology, Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.
Roberts
Brian S
BS
Berndt
Jason D
JD
Marine
Shane
S
Anastas
Jamie
J
Chung
Namjin
N
Ferrer
Marc
M
Yi
XianHua
X
Stoick-Cooper
Cristi L
CL
von Haller
Priska D
PD
Kategaya
Lorna
L
Chien
Andy
A
Angers
Stephane
S
MacCoss
Michael
M
Cleary
Michele A
MA
Arthur
William T
WT
Moon
Randall T
RT
D042501:Angiogenic Proteins / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D011485:Protein Binding; D025941:Protein Interaction Mapping; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000502:physiology*
C482200:AGGF1 protein, human; D042501:Angiogenic Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin