Tax1 enhances cancer cell proliferation via Ras–Raf–MEK–ERK signaling pathway

Erbin is an ErbB2 binding protein, which belongs to the LAP (leucine‐rich repeat (LRR) and PDZ domain) protein family. We previously reported that Tax1, a protein of the human T‐cell leukemia virus type I (HTLV‐I), associated with Erbin by using Erbin PDZ domain as a bait to screen a human T lymphocyte cDNA library by a yeast two hybrid strategy. In the present study, we demonstrated that Tax1 enhances cancer cell proliferation via Ras–Raf–MEK–ERK signaling pathway by using molecular section strategy. The pull‐down assay showed that the four amino acid domain, that is, Tax1 350–353, might specifically interact with Erbin, but not any other Tax1 deletion mutants. The coimmunoprecipitation assay confirmed that Tax1 350–353 domain bound with Erbin in vivo. Functional study demonstrated that overexpresssion of Tax1 in cancer cell lines of liver cancer SMMC‐7721, colon cancer HCT‐116, and breast cancer MCF‐7 facilitated the cell proliferation. And the transfection of Tax1 353 in MCF‐7 cells with endogenous Erbin expression markedly increased phosphorylation of Ras, Raf, MEK1/2, ERK1/2, PI3K, and IκBα, suggesting that Tax1‐enhanced cell proliferation tracks Ras–Raf–MEK–ERK signaling pathway. © 2009 IUBMB IUBMB Life, 61(6): 685–692, 2009