Human CPR (cell cycle progression restoration) genes impart a Far- phenotype on yeast cells.
Regulated cell cycle progression depends on the proper integration of growth control pathways with the basic cell cycle machinery. While many of the central molecules such as cyclins, CDKs, and CKIs are known, and many of the kinases and phosphatases that modify the CDKs have been identified, little is known about the additional layers of regulation that impinge upon these molecules. To identify new regulators of cell proliferation, we have selected for human and yeast cDNAs that when overexpressed were capable of specifically overcoming G1 arrest signals from the cell cycle branch of the mating pheromone pathway, while still maintaining the integrity of the transcriptional induction branch. We have identified 13 human CPR (cell cycle progression restoration) genes and 11 yeast OPY (overproduction-induced pheromone-resistant yeast) genes that specifically block the G1 arrest by mating pheromone. The CPR genes represent a variety of biochemical functions including a new cyclin, a tumor suppressor binding protein, chaperones, transcription factors, translation factors, RNA-binding proteins, as well as novel proteins. Several CPR genes require individual CLNs to promote pheromone resistance and those that require CLN3 increase the basal levels of Cln3 protein. Moreover, several of the yeast OPY genes have overlapping functions with the human CPR genes, indicating a possible conservation of roles.
Edwards
M C
MC
Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Liegeois
N
N
Horecka
J
J
DePinho
R A
RA
Sprague
G F
GF
Tyers
M
M
Elledge
S J
SJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002455:Cell Division; D002874:Chromosome Mapping; D000013:Congenital Abnormalities / Q000235:genetics; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins / Q000378:metabolism; D018076:DNA, Complementary; D004271:DNA, Fungal; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase; D017353:Gene Deletion; D018816:Genes, cdc; D050956:HSP40 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D000072235:Mating Factor; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones / Q000235:genetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D010641:Phenotype; D010675:Pheromones / Q000378:metabolism / Q000494:pharmacology; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics
C082719:CLN1 protein, S cerevisiae; C082721:CLN2 protein, S cerevisiae; C079895:CLN3 protein, S cerevisiae; C105199:CLN3 protein, human; D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D018076:DNA, Complementary; D004271:DNA, Fungal; C494645:DNAJA2 protein, human; C081353:FAR1 protein, S cerevisiae; D005656:Fungal Proteins; D050956:HSP40 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D010455:Peptides; D010675:Pheromones; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C070319:YDJ1 protein, S cerevisiae; D000072235:Mating Factor