Receptor for activated C-kinase 1 (RACK1) interacts with F-box and WD-repeat domain containing-2 (FBW2) to upregulate glial cell missing-1 (GCM1) stability and placental cell migration and invasion

In this study, we perform tandem affinity purification coupled with mass spectrometry analysis identifying RACK1 as an FBW2-interacting protein. RACK1 is a multifaceted scaffold protein containing seven WD repeats. We demonstrate that the WD repeats in both RACK1 and FBW2 are required for the interaction of RACK1 and FBW2. Furthermore, RACK1 competes with GCM1 for FBW2 and thereby prevents GCM1 ubiquitination, which is also supported by the observation that GCM1 is destabilized in RACK1-knockdown BeWo placental cells. Importantly, RACK1 knockdown leads to decreased expression of the GCM1 target gene high-temperature requirement protein A4 (HtrA4), which encodes a serine protease crucial for cell migration and invasion. As a result, migration and invasion activities are downregulated in RACK1-knockdown BeWo cells. Our study reveals a novel function for RACK1 to regulate GCM1 activity and placental cell migration and invasion.

Source: BJ Cell - May 7, 2013 Category: Biochemistry Authors: C Wang, H Lo, S Lin, H Chen Tags: BJ Signal Source Type: research