The mitotic feedback control gene MAD2 encodes the alpha-subunit of a prenyltransferase.
The mad2-1 mutation inactivates the cell-cycle feedback control that prevents budding yeast cells from leaving mitosis until spindle assembly is complete. The gene product of MAD2 shows significant sequence similarity to the alpha-subunit of prenyltransferases. Here we isolate a new temperature-sensitive mad2 mutant, mad2-2ts, and find that Mad2p is required for the membrane association of Ypt1p and Sec4p, two prenylated small GTP-binding proteins involved in protein trafficking. Extracts from mad2-2ts mutant cells fail to geranylgeranylate a number of substrates at the non-permissive temperature. mad2-2ts is synthetically lethal with bet2-1, a mutation in the gene that encodes for the beta-subunit of the Ypt1p and Sec4p geranylgeranyl transferase. Therefore MAD2 and BET2 gene products may physically interact to form a geranylgeranyl transferase complex. In addition, the difference between the phenotypes of mad2-1 and mad2-2ts suggests that MAD2 has distinct roles in protein transport and the mitotic feedback control.
Li
R
R
Department of Biochemistry, University of California, San Francisco 94143-0444.
Havel
C
C
Watson
J A
JA
Murray
A W
AW
D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000502:physiology; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003433:Crosses, Genetic; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D064246:Mad2 Proteins; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D017368:Protein Prenylation / Q000235:genetics* / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014166:Transferases / Q000235:genetics* / Q000378:metabolism; D020691:rab GTP-Binding Proteins
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; C577695:MAD2 protein, S cerevisiae; D064246:Mad2 Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D014166:Transferases; D019204:GTP-Binding Proteins; C060755:YPT1 protein, S cerevisiae; C064320:SEC4 protein, S cerevisiae; D020691:rab GTP-Binding Proteins