The retinoblastoma suppressor (Rb)-associated protein 46 (RbAp46) is a nuclear protein of the WD-repeat protein family and a component of the histone deacetylase complex that physically interacts with Rb. We demonstrated that RbAp46 is a gene up-regulated by the Wilms' tumor suppressor (WT1) and functions as a negative regulator of cell growth. Here we have investigated the ability of RbAp46 to inhibit malignant phenotype of adenovirus-transformed human embryonic kidney (HEK) 293 cells in tumorigenesis assays. We have found that expression of RbAp46 suppressed clonal growth of HEK 293 cells in soft agar and inhibited tumor growth of these cells in nude mice. Furthermore, expression of RbAp46 resulted in an increase of cells in the G2/M fraction of cell cycle and augmented apoptosis in serum-starved cells. The results suggest that high levels of RbAp46 expression inhibit the transformation of tumor cells through interfering with normal cell cycle and/or enhancing apoptotic cell death.
Copyright 2001 Wiley-Liss, Inc.