| Further , we identify the tumor suppressor WW domain containing oxidoreductase ( Wwox ) as an Ack 1 interacting protein . ^^^ Activated tyrosine kinase Ack 1 promotes prostate tumorigenesis : role of Ack 1 in polyubiquitination of tumor suppressor Wwox . ^^^ Activated Ack 1 tyrosine phosphorylated Wwox , leading to rapid dissociation of the Ack 1 Wwox complex and concomitant Wwox polyubiquitination followed by degradation . ^^^ Tyrosine phosphorylation of Wwox was critical for its degradation , as splice variant WwoxDelta 5 8 that was not phosphorylated by Ack 1 failed to undergo polyubiquitination and degradation . ^^^ We observed that Y33F Wwox mutant was still tyrosine phosphorylated and polyubiquitinated by Ack 1 action . ^^^ |