Dataset Information

Genetic analysis of CAND1-CUL1 interactions in Arabidopsis supports a role for CAND1-mediated cycling of the SCFTIR1 complex.

ABSTRACT: SKP1-Cullin1-F-box protein (SCF) ubiquitin-ligases regulate numerous aspects of eukaryotic growth and development. Cullin-Associated and Neddylation-Dissociated (CAND1) modulates SCF function through its interactions with the CUL1 subunit. Although biochemical studies with human CAND1 suggested that CAND1 plays a negative regulatory role by sequestering CUL1 and preventing SCF complex assembly, genetic studies in Arabidopsis have shown that cand1 mutants exhibit reduced SCF activity, demonstrating that CAND1 is required for optimal SCF function in vivo. Together, these genetic and biochemical studies have suggested a model of CAND1-mediated cycles of SCF complex assembly and disassembly. Here, using the SCF(TIR1) complex of the Arabidopsis auxin response pathway, we test the SCF cycling model with Arabidopsis mutant derivatives of CAND1 and CUL1 that have opposing effects on the CAND1-CUL1 interaction. We find that the disruption of the CAND1-CUL1 interaction results in an increased abundance of assembled SCF(TIR1) complex. In contrast, stabilization of the CAND1-CUL1 interaction diminishes SCF(TIR1) complex abundance. The fact that both decreased and increased CAND1-CUL1 interactions result in reduced SCF(TIR1) activity in vivo strongly supports the hypothesis that CAND1-mediated cycling is required for optimal SCF function.

SUBMITTER: Zhang W

PROVIDER: S-EPMC2448860 | biostudies-other | 2008 Jun

REPOSITORIES: biostudies-other

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Genetic analysis of CAND1-CUL1 interactions in Arabidopsis supports a role for CAND1-mediated cycling of the SCFTIR1 complex.

Zhang Wenjing W Ito Hironori H Quint Marcel M Huang He H Noël Laurent D LD Gray William M WM

Proceedings of the National Academy of Sciences of the United States of America 20080611 24

SKP1-Cullin1-F-box protein (SCF) ubiquitin-ligases regulate numerous aspects of eukaryotic growth and development. Cullin-Associated and Neddylation-Dissociated (CAND1) modulates SCF function through its interactions with the CUL1 subunit. Although biochemical studies with human CAND1 suggested that CAND1 plays a negative regulatory role by sequestering CUL1 and preventing SCF complex assembly, genetic studies in Arabidopsis have shown that cand1 mutants exhibit reduced SCF activity, demonstrati ...[more]

PMID: 18550827

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Project description:Production of heat via nonshivering thermogenesis (NST) is critical for temperature homeostasis in mammals. Uncoupling protein UCP1 plays a central role in NST by uncoupling the proton gradients produced in the inner membranes of mitochondria to produce heat; however, the extent to which UCP1 homologues, UCP2 and UCP3, are involved in NST is the subject of an ongoing debate. We used an evolutionary approach to test the hypotheses that variants that are associated with increased expression of these genes (UCP1 -3826A, UCP2 -866A, and UCP3 -55T) show evidence of adaptation with winter climate. To that end, we calculated correlations between allele frequencies and winter climate variables for these single-nucleotide polymorphisms (SNPs), which we genotyped in a panel of 52 worldwide populations. We found significant correlations with winter climate for UCP1 -3826G/A and UCP3 -55C/T. Further, by analyzing previously published genotype data for these SNPs, we found that the peak of the correlation for the UCP1 region occurred at the disease-associated -3826A/G variant and that the UCP3 region has a striking signal overall, with several individual SNPs showing interesting patterns, including the -55C/T variant. Resequencing of the regions in a set of three diverse population samples helped to clarify the signals that we found with the genotype data. At UCP1, the resequencing data revealed modest evidence that the haplotype carrying the -3826A variant was driven to high frequency by selection. In the UCP3 region, combining results from the climate analysis and resequencing survey suggest a more complex model in which variants on multiple haplotypes may independently be correlated with temperature. This is further supported by an excess of intermediate frequency variants in the UCP3 region in the Han Chinese population. Taken together, our results suggest that adaptation to climate influenced the global distribution of allele frequencies in UCP1 and UCP3 and provide an independent source of evidence for a role in cold resistance for UCP3.

Dataset Information

Genetic analysis of CAND1-CUL1 interactions in Arabidopsis supports a role for CAND1-mediated cycling of the SCFTIR1 complex.

Publications

Genetic analysis of CAND1-CUL1 interactions in Arabidopsis supports a role for CAND1-mediated cycling of the SCFTIR1 complex.

Similar Datasets

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