The phytohormone ethylene controls plant growth and stress responses. Ethylene-exposed dark-grown Arabidopsis seedlings exhibit dramatic growth reduction, yet the seedlings rapidly return to the basal growth rate when ethylene gas is removed. However, the underlying mechanism governing this acclimation of dark-grown seedlings to ethylene remains enigmatic. Here, we report that ethylene triggers the translocation of the Raf-like protein kinase CONSTITUTIVE TRIPLE RESPONSE1 (CTR1), a negative regulator of ethylene signaling, from the endoplasmic reticulum to the nucleus. Nuclear-localized CTR1 stabilizes the ETHYLENE-INSENSITIVE3 (EIN3) transcription factor by interacting with and inhibiting EIN3-BINDING F-box (EBF) proteins, thus enhancing the ethylene response and delaying growth recovery. Furthermore, Arabidopsis plants with enhanced nuclear-localized CTR1 exhibited improved tolerance to drought and salinity stress. These findings uncover a mechanism of the ethylene signaling pathway that links the spatiotemporal dynamics of cellular signaling components to physiological responses.

Ethylene gas controls plant growth and stress responses. Ethylene-exposed dark-grown seedlings exhibit a dramatic growth reduction, yet the seedlings rapidly return to the basal growth rate when ethylene gas is removed. However, the underlying mechanism governing this remarkable reversible acclimation of dark-grown seedlings to ethylene remains enigmatic. Here, 5 we report that ethylene triggers the translocation of the Raf-like protein kinase CONSTITUTIVE TRIPLE RESPONSE1 (CTR1), a negative regulator of ethylene signaling, from the endoplasmic reticulum to the nucleus. Nuclear-localized CTR1 inhibits the ETHYLENE-INSENSITIVE3 (EIN3) transcription factor via the EIN3-BINDING F-box Proteins, resulting in rapid suppression of the ethylene response, thus promoting fast growth recovery. These findings uncover a 10 mechanism of the ethylene signaling pathway that links the spatiotemporal dynamics of cellular signaling components to organismal responses. 15 20 25 3 Introduction:The ability of organisms to respond to and integrate environmental signals leading to an appropriate response is critical for optimal growth and development, particularly for plants, which are non-motile. Plants adapt to a wide variety of abiotic stresses, and upon removal of stress, they need to rapidly restore basal cellular homeostasis. One key signal for abiotic stress 5 is the plant hormone ethylene. Ethylene is involved in multiple aspects of growth and development, including fruit ripening, leaf and floral senescence, cell elongation, seed germination, and root hair formation, as well as responses to biotic and abiotic stress 1-3 .Ethylene-mediated stress acclimation includes, but is not limited to, the rapid elongation of rice internodes in response to flooding, drought responses, salt tolerance, heavy metal tolerance, 10 and morphological changes of roots in response to nutrient deficiency 4-8 . How ethylene regulates such remarkable plasticity of plant stress adaptation is poorly understood, however.Extensive molecular genetic studies have elucidated the basic ethylene signaling pathway 2, 9-12 . In the absence of ethylene, the endoplasmic reticulum (ER)-localized ethylene receptors activate the CTR1 protein kinase, which in turn phosphorylates Ethylene-Insensitive 2 15 (EIN2), an ER membrane-localized Nramp homolog that positively regulates ethylene responses. CTR1-mediated phosphorylation of EIN2 leads to its ubiquitination and proteolysis by the 26S proteasome [11][12][13][14][15][16][17][18] . In response to ethylene, the receptors, and hence CTR1, are inactivated, leading to reduced phosphorylation and increased accumulation of EIN2. EIN2 is then proteolytically cleaved, releasing the C-terminal domain (EIN2-CEND) which translocates 20 into the nucleus where it activates the Ethylene-Insensitive 3 (EIN3) and EIN3-Like (EIL) paralogs which function as central transcription factors in ethylene signaling [16][17][18] . EIN2-CEND also associates with the EIN3-Binding F-box 1 (EBF1) and EBF2 mRNAs and represses their translation, thus ...