The Experts below are selected from a list of 3450 Experts worldwide ranked by ideXlab platform

Xiaoping Shen - One of the best experts on this subject based on the ideXlab platform.

Zheng Xu - One of the best experts on this subject based on the ideXlab platform.

Chengting Chien - One of the best experts on this subject based on the ideXlab platform.

  • the proto oncogene int6 is essential for neddylation of CUL1 and cul3 in drosophila
    PLOS ONE, 2008
    Co-Authors: Sigal Rencuslazar, Chengting Chien, Junetai Wu, Yaniv Amir, Daniel Chamovitz, Daniel L Segal
    Abstract:

    Int6 is a proto-oncogene implicated in various types of cancer, but the mechanisms underlying its activity are not clear. Int6 encodes a subunit of the eukaryotic translation initiation factor 3, and interacts with two related complexes, the proteasome, whose activity is regulated by Int6 in S. pombe, and the COP9 signalosome. The COP9 signalosome regulates the activity of Cullin-Ring Ubiquitin Ligases via deneddylation of their cullin subunit. We report here the generation and analysis of two Drosophila mutants in Int6. The mutants are lethal demonstrating that Int6 is an essential gene. The mutant larvae accumulate high levels of non-neddylated CUL1, suggesting that Int6 is a positive regulator of cullin neddylation. Overexpression in Int6 in cell culture leads to accumulation of neddylated cullins, further supporting a positive role for Int6 in regulating neddylation. Thus Int6 and the COP9 signalosome play opposing roles in regulation of cullin neddylation.

  • neddylation and deneddylation regulate CUL1 and cul3 protein accumulation
    Nature Cell Biology, 2005
    Co-Authors: Junetai Wu, Chengting Chien, Yenchen Hu
    Abstract:

    Cullin family proteins organize ubiquitin ligase (E3) complexes to target numerous cellular proteins for proteasomal degradation. Neddylation, the process that conjugates the ubiquitin-like polypeptide Nedd8 to the conserved lysines of cullins, is essential for in vivo cullin-organized E3 activities1,2. Deneddylation, which removes the Nedd8 moiety, requires the isopeptidase activity of the COP9 signalosome (CSN)3,4. Here we show that in cells deficient for CSN activity, cullin1 (CUL1) and cullin3 (Cul3) proteins are unstable, and that to preserve their normal cellular levels, CSN isopeptidase activity is required. We further show that neddylated CUL1 and Cul3 are unstable — as suggested by the evidence that Nedd8 promotes the instability of both cullins — and that the unneddylatable forms of cullins are stable. The protein stability of Nedd8 is also subject to CSN regulation and this regulation depends on its cullin-conjugating ability, suggesting that Nedd8-conjugated cullins are degraded en bloc. We propose that while Nedd8 promotes cullin activation through neddylation, neddylation also renders cullins unstable. Thus, CSN deneddylation recycles the unstable, neddylated cullins into stable, unneddylated ones, and promotes cullin-organized E3 activity in vivo.

  • CUL1 and cul3 mediate distinct protein degradation mechanisms to control ci stability in drosophila eye development
    Journal of Genetics and Molecular Biology, 2002
    Co-Authors: Chanyen Ou, Yingjiun Chen, Chengting Chien
    Abstract:

    The ubiquitin-like protein, Nedd8, covalently modifies members of the Cullin family. Cullins are the major components of a series of ubiquitin ligases that control the degradation of a broad range of proteins. We found that Nedd8 modifies Cul 1 in Drosophila. In Drosophila Nedd8 and Cul 1 mutants, protein levels of the signal transduction effectors, Cubitus nterruptus (Ci) and Armadillo (Arm), and the cell cycle regulator, Cyclin E (CycE), are highly accumulated, suggesting that the Cul I-based SCF complex requires Nedd8 modification for the degradation processes of Ci, Arm, and CycE in vivo. We further show that two distinct degradation mechanisms odulating Ci stability in the developing eye disc are separated by the morphogenetic furrow (MF) in which retinal differentiation is initiated. In cells anterior to the MF, Ci proteolytic processing promoted by PKA requires the activity of the Nedd8-modified Cull-based SCFslimb complex. In the posterior cells, Ci degradation is controlled by a mechanism that requires the activity of Cul 3, another member of the Cullin family. This posterior Ci degradation mechanism, which partially requires Nedd8 modification, is activated by hedgehog (Hh) signaling and PKA-independent.

  • distinct protein degradation mechanisms mediated by CUL1 and cul3 controlling ci stability in drosophila eye development
    Genes & Development, 2002
    Co-Authors: Chanyen Ou, Yingjiun Chen, Chengting Chien
    Abstract:

    The ubiquitin-like protein, Nedd8, covalently modifies members of the Cullin family. Cullins are the major components of a series of ubiquitin ligases that control the degradation of a broad range of proteins. We found that Nedd8 modifies CUL1 in Drosophila .I nDrosophila Nedd8 and CUL1 mutants, protein levels of the signal transduction effectors, Cubitus interruptus (Ci) and Armadillo (Arm), and the cell cycle regulator, Cyclin E (CycE), are highly accumulated, suggesting that the CUL1-based SCF complex requires Nedd8 modification for the degradation processes of Ci, Arm, and CycE in vivo. We further show that two distinct degradation mechanisms modulating Ci stability in the developing eye disc are separated by the morphogenetic furrow (MF) in which retinal differentiation is initiated. In cells anterior to the MF, Ci proteolytic processing promoted by PKA requires the activity of the Nedd8-modified CUL1-based SCF Slimb complex. In posterior cells, Ci degradation is controlled by a mechanism that requires the activity of Cul3, another member of the Cullin family. This posterior Ci degradation mechanism, which partially requires Nedd8 modification, is activated by Hedgehog (Hh) signaling and is PKA-independent.

Kaibei Yu - One of the best experts on this subject based on the ideXlab platform.

Kotaro T Yamamoto - One of the best experts on this subject based on the ideXlab platform.

  • A new temperature-insensitive allele of the Arabidopsis AXR6/CUL1 locus derived from a missense mutation in the C-terminal RBX1 binding region.
    Plant Signaling & Behavior, 2015
    Co-Authors: Yukiko Mori, Makoto Hayashi, Mikio Nishimura, Kotaro T Yamamoto
    Abstract:

    We isolated a new recessive allele at the AUXIN RESISTANT6/CULLIN1 (AXR6/CUL1) locus, axr6–101, from an EMS-mutagenized population of Arabidopsis thaliana, the Landsberg erecta ecotype. axr6–101 is auxin resistant and semi-dwarf similar to the other recessive axr6 mutants. The axr6–101 phenotype is caused by the E716K substitution of the CUL1 protein, which is likely to affect its ability to bind to the C-terminal RING domain of RING-box 1 (RBX1). The previously reported allele of AXR6, CUL1–7, is caused by a substitution at T510 that binds to the N-terminal β-strand of RBX1. Although CUL1–7 shows temperature-sensitive phenotype, the axr6–101 phenotype is largely unaffected by temperature. axr6–101 may provide an important genetic resource for study of the structure−function relationship of the CUL1 protein.

  • a new temperature insensitive allele of the arabidopsis axr6 CUL1 locus derived from a missense mutation in the c terminal rbx1 binding region
    Plant Signaling & Behavior, 2015
    Co-Authors: Yukiko Mori, Makoto Hayashi, Mikio Nishimura, Kotaro T Yamamoto
    Abstract:

    We isolated a new recessive allele at the AUXIN RESISTANT6/CULLIN1 (AXR6/CUL1) locus, axr6–101, from an EMS-mutagenized population of Arabidopsis thaliana, the Landsberg erecta ecotype. axr6–101 is auxin resistant and semi-dwarf similar to the other recessive axr6 mutants. The axr6–101 phenotype is caused by the E716K substitution of the CUL1 protein, which is likely to affect its ability to bind to the C-terminal RING domain of RING-box 1 (RBX1). The previously reported allele of AXR6, CUL1–7, is caused by a substitution at T510 that binds to the N-terminal β-strand of RBX1. Although CUL1–7 shows temperature-sensitive phenotype, the axr6–101 phenotype is largely unaffected by temperature. axr6–101 may provide an important genetic resource for study of the structure−function relationship of the CUL1 protein.