SLy2 targets the nuclear SAP30/HDAC1 complex.
The adapter protein SLy2 (SH3 protein expressed in lymphocytes 2), also named HACS1, NASH1 or SAMSN1, is expressed in hematopoietic tissues, muscle, heart, brain, lung, pancreas, endothelial cells and myelomas. Endogenous SLy2 expression was shown to be upregulated in primary B cells upon differentiation and proliferation-inducing stimuli, and transduction experiments suggest a stimulatory role for SLy2 in B cell differentiation to plasma cells. However the signalling pathways regulated by SLy2 remain unknown. In this study we identify novel interaction partners of SLy2 providing a molecular framework for its function. We show that phosphorylated SLy2 directly interacts with 14-3-3 proteins via a previously unrecognized phosphorylation site. Furthermore, we demonstrate that 14-3-3 proteins control nucleo-cytoplasmic shuttling of SLy2 by retaining phosphorylated SLy2 in the cytoplasm. In the nucleus, SLy2 interacts with the SAP30/HDAC1 complex and regulates the activity of HDAC1. Thus, our findings unravel a novel mechanism how SLy2 localization is controlled and implicate SLy2 in the epigenetic control of gene expression.
Brandt
Simone
S
Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine University Duesseldorf, Germany.
Ellwanger
Kornelia
K
Beuter-Gunia
Cornelia
C
Schuster
Marc
M
Hausser
Angelika
A
Schmitz
Ingo
I
Beer-Hammer
Sandra
S
D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D019169:Jurkat Cells; D010766:Phosphorylation; D020798:Two-Hybrid System Techniques
D048948:14-3-3 Proteins; D033942:Adaptor Proteins, Vesicular Transport; C435526:SAMSN1 protein, human; C113294:SAP30 protein, human; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases