Mechanisms of nuclear localization of the progesterone receptor: evidence for interaction between monomers.

Area of Science:

• Molecular Biology
• Cell Biology
• Endocrinology

Background:

• The progesterone receptor (PR) is a crucial nuclear receptor regulating gene expression in response to progesterone.
• Understanding the mechanisms of PR nuclear localization is essential for comprehending its role in various physiological and pathological processes.

Purpose of the Study:

• To elucidate the distinct mechanisms governing the nuclear import and localization of the rabbit progesterone receptor.
• To identify specific regions and interactions responsible for PR translocation into the nucleus.

Main Methods:

• Construction and analysis of deletion mutants of the rabbit progesterone receptor.
• Utilizing monoclonal antibodies to track receptor localization within cells.
• Investigating receptor behavior in the presence and absence of hormone ligands.

Main Results:

• A constitutively active nuclear localization signal was identified between amino acids 638-642.
• Deletion of this signal sequence resulted in cytoplasmic localization, with hormone enabling nuclear import.
• Hormone binding induced dimerization and nuclear translocation of both cytoplasmic and nuclear PR monomers via their steroid binding domains.

Conclusions:

• The rabbit progesterone receptor utilizes at least two independent pathways for nuclear localization.
• A signal sequence mediates constitutive nuclear import, while ligand binding activates a hormone-dependent mechanism involving receptor dimerization and nuclear transfer.