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Anatomy of the Steroid Receptor Zinc Finger Region

Cell Biology and Genetics Program, Sloan-Kettering Institute New York, New York 10021

Correspondence: Address requests for reprints to: Leonard P. Freedman, Ph.D., Cell Biology and Genetics Program, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021.

Abstract

I. Introduction: LIKE many transcriptional regulatory proteins, nuclear hormone receptors are single polypeptides that are organized into relatively discrete functional domains (1). This common domain organization groups these receptors into a superfamily of functionally and most likely structurally related, hormonally regulable, transcription factors. The superfamily includes receptors for steroid hormones, such as glucocorticoids, progesterone, estrogen, aldosterone, and androgens, as well as hormonal forms of vitamins A and D, thyroid hormone, and peroxisomal activators (2–6). Several other receptorlike proteins whose ligands have yet to be identified have recently been isolated utilizing molecular cloning techniques. In the same way, several putative nuclear receptors from Drosophila that appear to act as regulators of early development (Refs. 7–10; reviewed in Ref. 11) have been identified, including a receptor for the insect steroid ecdysone (12).

Upon association with a particular ligand, nuclear receptors, as soluble intracellular proteins, bind to specific DNA sites generally located upstream of responsive genes, and up- or down-regulate the transcription of those genes (13), presumably by functionally interacting with other components of the transcriptional apparatus. Domains for ligand binding (located in the carboxyterminal region), DNA binding (located toward the central or amino terminus), nuclear localization (within both the DNA- and ligand binding domains), and transcriptional modulation (localized to more variable regions of the receptors, including the N terminus) (Fig. 1) all can confer their specific functions when linked to unrelated, nonreceptor proteins (14–19). In addition, a putative dimerization region has been described that overlaps part of the ligand binding domain for some receptors (20–22).

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