Yop1p, the yeast homolog of the polyposis locus protein 1, interacts with Yip1p and negatively regulates cell growth

Rab proteins are small GTPases that are essential elements of the protein t ransport machinery of eukaryotic cells. Each round of membrane transport re quires a cycle of Rab protein nucleotide binding and hydrolysis. We have re cently characterized a protein, Yip1p, which appears to play a role in Rab- mediated membrane transport in Saccharomyces cerevisiae. In this study, we report the identification of a Yip1p-associated protein, Yop1p. Yop1p is a membrane protein with a hydrophilic region at its N terminus through which it interacts specifically with the cytosolic domain of Yip1p. Yop1p could a lso be coprecipitated with Rab proteins from total cellular lysates. The TB 2 gene is the human homolog of Yop1p (Rinzler, K. W., Nilbert, M. C., Su, L .-K., Vogelstein, B., Bryan, T. M., Levey, D. B., Smith, K. J., Preisinger, A. C., Hedge, P., McKechnie, D., Finniear, R., Markham, A., Groffen, J., B oguski, M. S., Altschul, S. F., Horii, A., Ando, H. M., Y., Miki, Y., Nishi sho, I., and Nakamura, Y. (1991) Science 258, 661-665). Our data demonstrat e that Yop1p negatively regulates cell growth. Disruption of YOP1 has no ap parent effect on cell viability, while overexpression results in cell death , accumulation of internal cell membranes, and a block in membrane traffic. These results suggest that Yop1p acts in conjunction with Yip1p to mediate a common step in membrane traffic.