Dominant effector genetics in mammalian cells.
We have expressed libraries of peptides in mammalian cells to select for trans-dominant effects on intracellular signaling systems. As an example-and to reveal pharmacologically relevant points in pathways that lead to Taxol resistance-we selected for peptide motifs that confer resistance to Taxol-induced cell death. Of several peptides selected, one, termed RGP8.5, was linked to upregulation of expression of the gene ABCB1 (also known as MDR1, for multiple drug resistance) in HeLa cells. Our data indicate that trans-dominant effector peptides can point to potential mechanisms by which signaling systems operate. Such tools may be useful in functional genomic analysis of signaling pathways in mammalian disease processes.
Xu
X
X
Rigel, Inc., San Francisco, California, USA. xxu@rigel.com
Leo
C
C
Jang
Y
Y
Chan
E
E
Padilla
D
D
Huang
B C
BC
Lin
T
T
Gururaja
T
T
Hitoshi
Y
Y
Lorens
J B
JB
Anderson
D C
DC
Sikic
B
B
Luo
Y
Y
Payan
D G
DG
Nolan
G P
GP
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005799:Genes, Dominant / Q000235:genetics; D019450:Genes, MDR / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000187:drug effects*; D020798:Two-Hybrid System Techniques; D015854:Up-Regulation / Q000187:drug effects*
D009097:Multienzyme Complexes; D019151:Peptide Library; D010455:Peptides; D021122:Protein Subunits; D012333:RNA, Messenger; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D017239:Paclitaxel