Bau, a Splice Form of Neurabin-I that Interacts with the Tumor Suppressor Bin1, Inhibits Malignant Cell Transformation

Abstract

Bin1 is a nucleocytoplasmic adaptor protein and tumor suppressor. A novel protein termed Bau was identified through its ability to interact with a region of Bin1 required to inhibit malignant cell transformation by certain oncogenes. Bau is a splice form of Neurabin-I, one of two related F-actin-binding proteins that are proposed to link cadherin-based cell-cell adhesion sites with the growth regulatory kinase p70^S6K. Bau lacks actin- and p70^S6K-binding domains found in Neurabin-1 but includes coiled-coil domains that are part of its central domain as well as additional sequences not found in Neurabin-1. Interaction with Bin1 requires the presence of the U3 region which is alternately spliced in muscle cells. Bau localizes to the nucleus and cytosol. Like Bin1, Bau can suppress oncogene-mediated transformation and inhibit tumor cell growth. We suggest that Bau may link Bin1 to the Neurabin-1/p70^S6K system in muscle and other cells, perhaps providing a mechanism to influence adhesion-dependent signals which affect cell fate.

Key Words:

• Transformation
• tumor suppressor
• Myc
• adhesion