Characterization of the hormone-binding domain of the chicken c-erbA/thyroid hormone receptor protein.

TY - JOUR

T1 - Characterization of the hormone-binding domain of the chicken c-erbA/thyroid hormone receptor protein.

AU - Muñoz, A

AU - Zenke, M

AU - Gehring, U

AU - Sap, J

AU - Beug, H

AU - Vennström, B

N1 - Keywords: Animals; Chickens; Chimera; Cloning, Molecular; Genes; Kinetics; Mutation; Plasmids; Protein Biosynthesis; Proto-Oncogenes; Receptors, Thyroid Hormone; Recombinant Proteins; Thyroid Hormones; Transcription, Genetic

PY - 1988

Y1 - 1988

N2 - To identify and characterize the hormone-binding domain of the thyroid hormone receptor, we analyzed the ligand-binding capacities of proteins representing chimeras between the normal receptor and P75gag-v-erbA, the retrovirus-encoded form deficient in binding ligand. Our results show that several mutations present in the carboxy-terminal half of P75gag-v-erbA co-operate in abolishing hormone binding, and that the ligand-binding domain resides in a position analogous to that of steroid receptors. Furthermore, a point mutation that is located between the putative DNA and ligand-binding domains of P75gag-v-erbA and that renders it biologically inactive fails to affect hormone binding by the c-erbA protein. These results suggest that the mutation changed the ability of P75gag-v-erbA to affect transcription since it also had no effect on DNA binding. Our data also suggest that hormone-independent activity of P75gag-v-erbA provided a selective advantage to the avian erythroblastosis virus during the original selection for a highly oncogenic strain of the virus.

AB - To identify and characterize the hormone-binding domain of the thyroid hormone receptor, we analyzed the ligand-binding capacities of proteins representing chimeras between the normal receptor and P75gag-v-erbA, the retrovirus-encoded form deficient in binding ligand. Our results show that several mutations present in the carboxy-terminal half of P75gag-v-erbA co-operate in abolishing hormone binding, and that the ligand-binding domain resides in a position analogous to that of steroid receptors. Furthermore, a point mutation that is located between the putative DNA and ligand-binding domains of P75gag-v-erbA and that renders it biologically inactive fails to affect hormone binding by the c-erbA protein. These results suggest that the mutation changed the ability of P75gag-v-erbA to affect transcription since it also had no effect on DNA binding. Our data also suggest that hormone-independent activity of P75gag-v-erbA provided a selective advantage to the avian erythroblastosis virus during the original selection for a highly oncogenic strain of the virus.

M3 - Journal article

C2 - 3359993

SN - 0261-4189

VL - 7

SP - 155

EP - 159

JO - E M B O Journal

JF - E M B O Journal

IS - 1

ER -