Light signals from the environment are perceived by distinct classes of photoreceptors and transduced to nuclear regulators to control developmental programs, in cooperation with developmental and other environmental cues. The long-term goal of my NIH funded research (now in year 22, R37-GM047850) is to fully understand the cellular and biochemical basis of light control network in plant development. Our ongoing NIH sponsored investigation has so far revealed an overall framework of three evolutionarily conserved multisubunit protein complexes (COP1-SPA complex or COP1 complex, COP10-DET1-DDB1 or CDD complex, and COP9 signalosome or CSN), whose key subunits were initially identified by our genetic analysis of the COP/DET/FUS loci in Arabidopsis. We have revealed the subunit composition and established that those three complexes largely act to modulate the stability and/or activity of specific transcription factors (including HY5 and HYH) that promote photomorphogenesis. While the COP1 complex and the CDD complex can collaborate with CUL4 to form large E3 complexes, CSN is a modulator of all Cullin-RING family of E3s. A number of major advances have been made about how light signals modulate changes in protein interaction landscape of these complexes and transcription factors, achieving signal-dependent regulation of gene expression. Here I propose four main aims to continue this NIH-sponsored research, which will address a number of general mechanistic issues that governs the light-regulated developmental switch, taking advantage of the knowledge and reagents developed from our previous and ongoing studies. Specifically, the proposed four main aims will cover three complementary aspects of further research. The first aspect, Aim 1, intends to identify novel modulators of COP1, which is expected to reveal new mechanistic insight on how COP1 is regulated with regard to its abundance, subcellular localization, and activity. The second aspect, including Aims 2 and 3, is to characterize the fundamental structural and biochemical basis of how COP1 and CDD complexes work and be regulated by distinct light stimuli. The third aspect, Aim 4, is to reveal the transcriptional network and the molecular action that govern a typical light-regulated developmental switch: photomorphogenesis vs skotomorphogenesis. The accomplishment of these proposed aims shall provide a comprehensive view of the regulatory network and fundamental mechanism essential for light control of development. Parts of our research findings on Arabidopsis may provide clues or even serve as guidance for investigating the roles of respective human counterparts of these protein complexes in human diseases.
Our ongoing NIH sponsored investigation has so far revealed an overall framework of three evolutionarily conserved multisubunit protein complexes (COP1-SPA complex or COP1 complex, COP10-DET1-DDB1 or CDD complex, and COP9 signalosome or CSN), whose key subunits were initially identified by our genetic analysis of the COP/DET/FUS loci. These three complexes largely act to modulate the stability and/or activity of specific transcription factors in light and hormonal signaling pathways. The three complexes also have counterparts in humans, and the related biomedical studies have revealed their roles in tumorigenesis, lipid metabolism, cardiovascular functions and immune responses, which underscore the impact of our plant research toward better understanding of human health. Our future studies on the structures, regulatory mechanisms, and discovery of new regulatory components of those complexes will continue to provide guiding principles for parallel human health research.
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