Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic checkpoint protein MAD1

Dong Yan Jin, Forrest Spencer, Kuan Teh Jeang

Research output: Contribution to journalArticlepeer-review

Abstract

In searching for cellular targets of the HTLV-I oncoprotein Tax, we identified TXBP181, which we characterized as the human homolog of yeast mitotic checkpoint MAD1 protein. Evidence supporting TXBP181 as HsMAD1 includes sequence conservation with yeast MAD1, hyperphosphorylation during S/G2/M phases and upon treatment of cells with nocodazole, and binding to HsMAD2. HsMAD1 functions as a homodimer. It localizes to the centrosome during metaphase and to the spindle midzone and the midbody during anaphase and telophase. Expression of either Tax or a transdominant-negative TXBP181 results in multinucleated cells, a phenotype consistent with a loss of HsMAD1 function. We propose a model of viral transformation in which Tax targets TXBP181, thereby abrogating a mitotic checkpoint.

Original languageEnglish (US)
Pages (from-to)81-91
Number of pages11
JournalCell
Volume93
Issue number1
DOIs
StatePublished - Apr 3 1998

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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