MCB 9507001 Bin-Tao Pan Ras, a small GTP binding protein, plays a pivotal role in cellular proliferation, differentiation, development, and transformation. Elucidation of how Ras controls the cell cycle is important in understanding how Ras regulates these cellular processes. In this project the Xenopus egg system is used to study how permanently active Ras (oncogenic Ras) controls the cell cycle. Oncogenic Ras induces chromatin changes, inhibits cdc2 kinase, and blocks or delays the progression of the cell cycle into M-phase. This project will test the hypothesis that oncogenic Ras persistently activates a 96 kD histone kinase which then feeds back to inhibit cdc2 kinase and results in arrest of the cell cycle. To address this hypothesis the gene coding for the 96 kD histone kinase will be cloned and full length transcripts from cDNA will be used to test whether chromatin changes, inhibition of cdc2 and arrest of the cell cycle can be induced. In addition, the cDNA will be used for structural and functional analysis of the 96 kD kinase. %%% This project investigates how the process of cell division is regulated from outside the cell by mechanisms associated with the outer membrane of the cell. The mechanism of transducing information that regulates cell division through the cells outer membrane is poorly understood. GTP binding proteins (the Ras protein employed in this project) represent one intracellular component thought to have a role. Consequently, examination of the function of the Ras protein in cells is likely in increase our understanding of how cell division is regulated. ***