Hormone signaling through protein destruction: a lesson from plants

Abstract

Ubiquitin-dependent protein degradation has emerged as a major pathway regulating eukaryotic biology. By employing a variety of ubiquitin ligases to target specific cellular proteins, the ubiquitin-proteasome system controls physiological processes in a highly regulated fashion. Recent studies on a plant hormone auxin have unveiled a novel paradigm of signal transduction in which ubiquitin ligases function as hormone receptors. Perceived by the F-box protein subunit of the SCF(TIR1) ubiquitin ligase, auxin directly promotes the recruitment of a family of transcriptional repressors for ubiquitination, thereby activating extensive transcriptional programs. Structural studies have revealed that auxin functions through a "molecular glue" mechanism to enhance protein-protein interactions with the assistance of another small molecule cofactor, inositol hexakisphosphate. Given the extensive repertoire of similar ubiquitin ligases in eukaryotic cells, this novel and widely adopted hormone-signaling mechanism in plants may also exist in other organisms.

Fig. 1.

The Skp1-Cullin1-F-box transport inhibitor response protein 1 (SCF^TIR1) ubiquitin ligase functions as the receptor for the plant hormone auxin. A: chemical structures of the natural auxin, 2 auxin analogs [2,4-dichlorophenoxyacetic acid (2,4-D) and 1-naphthalene acetic acid (1-NAA)], and jasmonate-isoleucine (JA-Ile). B: the role of SCF^TIR1 ubiquitin ligase in the auxin-signaling pathway in plants. In the absence of auxin, auxin/indole-3-acetic acids (AUX/IAAs) repress the expression of auxin response genes (AuxRE) by binding to the transcription activator auxin response factors (ARFs) (left). In the presence of auxin, the multisubunit SCF^TIR1 ubiquitin ligase recognizes the hormone and promotes the polyubiquitination and proteasomal degradation of AUX/IAAs in a hormone-dependent manner (middle). Auxin-induced degradation of AUX/IAAs frees ARFs, which activate the transcription of auxin response genes (right). U, ubiquitin protein.

Fig. 2.

The structure and mechanism of auxin action. A: crystal structure of Arabidopsis SKP1 (ASK1)-TIR1-inositol hexakisphosphate (IP6) in complex with auxin and an AUX/IAA domain II peptide. Both ASK1 (magenta) and TIR1 (blue) are shown in ribbon. Auxin is shown in space-filled model (green and red spheres). The AUX/IAA peptide (orange) and IP6 (red) are shown in sticks. B: a schematic diagram showing how auxin is sensed by TIR1 with the assistance of IP6 and how the hormone promotes TIR1-AUX/IAA interactions. LRRs, leucine-rich repeats.