Rig-G negatively regulates SCF-E3 ligase activities by disrupting the assembly of COP9 signalosome complex

Xu, Gui-Ping; Zhang, Zhanglin; Xiao, Shu Dong; Zhuang, Likun; Xia, Di; Zou, Qingping; Jia, Pei-Min; Tong, Jianhua

doi:10.1016/j.bbrc.2013.01.132

Cited by 10 publications

(11 citation statements)

References 29 publications

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“…In the case of Rig-G it is proposed that the protein recruits CSN subunits to the cytoplasm and thereby interferes with CSN assembly in the nucleus (Xu et al, 2013). …”

Section: Csn Promotes Cullin Deneddylationmentioning

confidence: 99%

The NEDD8 modification pathway in plants

Mergner

Schwechheimer

2014

Front. Plant Sci.

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NEDD8, in plants and yeasts also known as RELATED TO UBIQUITIN (RUB), is an evolutionarily conserved 76 amino acid protein highly related to ubiquitin. Like ubiquitin, NEDD8 can be conjugated to and deconjugated from target proteins, but unlike ubiquitin, NEDD8 has not been reported to form chains similar to the different polymeric ubiquitin chains that have a role in a diverse set of cellular processes. NEDD8-modification is best known as a post-translational modification of the cullin subunits of cullin-RING E3 ubiquitin ligases. In this context, structural analyses have revealed that neddylation induces a conformation change of the cullin that brings the ubiquitylation substrates into proximity of the interacting E2 conjugating enzyme. In turn, NEDD8 deconjugation destabilizes the cullin RING ligase complex allowing for the exchange of substrate recognition subunits via the exchange factor CAND1. In plants, components of the neddylation and deneddylation pathway were identified based on mutants with defects in auxin and light responses and the characterization of these mutants has been instrumental for the elucidation of the neddylation pathway. More recently, there has been evidence from animal and plant systems that NEDD8 conjugation may also regulate the behavior or fate of non-cullin substrates in a number of ways. Here, the current knowledge on NEDD8 processing, conjugation and deconjugation is presented, where applicable, in the context of specific signaling pathways from plants.

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“…In the case of Rig-G it is proposed that the protein recruits CSN subunits to the cytoplasm and thereby interferes with CSN assembly in the nucleus (Xu et al, 2013). …”

Section: Csn Promotes Cullin Deneddylationmentioning

confidence: 99%

The NEDD8 modification pathway in plants

Mergner

Schwechheimer

2014

Front. Plant Sci.

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“…Kip1 and induced morphologic features of partial differentiation in the human leukemic cell line U937 (Xiao et al, 2006;Xu et al, 2013). Of particular interest, in relation to our study, is that a small EF-hand Ca 2+ -binding protein psoriasin (also known as S100A7) has been shown to interact with CSN5 in breast cancer cells.…”

Section: Discussionmentioning

confidence: 69%

Regulation of Cop9 signalosome activity by the EF-hand Ca2+-binding protein tescalcin

Levay

Slepak

2014

Journal of Cell Science

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The Ca 2+ -binding protein tescalcin is known to be involved in hematopoietic cell differentiation; however, this mechanism is poorly understood. Here, we identify CSN4 (subunit 4 of the COP9 signalosome) as a novel binding partner of tescalcin. The COP9 signalosome (CSN) is a multiprotein complex that is essential for development in all eukaryotes. This interaction is selective, Ca 2+ -dependent and involves the PCI domain of CSN4 subunit. We then investigated tescalcin and CSN activity in human erythroleukemia HEL and promyelocytic leukemia K562 cells and find that phorbol 12-myristate 13-acetate (PMA)-induced differentiation, resulting in the upregulation of tescalcin, coincides with reduced deneddylation of cullin-1 (Cul1) and stabilization of p27Kip1 -molecular events that are associated with CSN activity. The knockdown of tescalcin led to an increase in Cul1 deneddylation, expression of F-box protein Skp2 and the transcription factor c-Jun, whereas the levels of cell cycle regulators p27 Kip1 and p53 decreased. These effects are consistent with the hypothesis that tescalcin might play a role as a negative regulator of CSN activity towards Cul1 in the process of induced cell differentiation.

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“…The following primary antibodies were used in this study: rabbit polyclonal anti- Rig-G antibody was described previously 11 ; anti-Cul 1 was obtained from Invitrogen (Grand Island, NY); anti-Cul 3 was purchased from BD (Franklin Lakes, NJ); anti-DAPK1 was produced by Sigma (St. Louis, MO); antibodies against LC3, NAE1, p27 kip , p-Beclin1 and βTrCP were from Cell Signaling Technologies Inc. (Beverly, MA); anti-NEDD8 was purchased from Abcam (Cambridge, UK); anti-UBE2M and β-actin were from ABclonal (USA); anti-DEPTOR and Skp2 antibodies, anti-mouse IgG, and anti-rabbit IgG were obtained from Santa Cruz Biotechnology Inc. (USA); anti-Beclin1 and KLHL20 were produced by Abgent (USA).…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, CRL-NEDD8 controls a high proportion of ubiquitylation events in cells, making this pathway an attractive target for pharmacological manipulation. Recent studies show that retinoic acid-induced gene G (Rig-g), first identified from an APL cell line NB4 treated with ATRA, is able to negatively regulate SCF-E3 ligase activities and largely decrease protein levels of cullin1 and β-TrCP, indicating a significant role for inhibition of CRL-NEDD8 pathway in the ATRA-induced APL differentiation 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

Inhibition of CRL-NEDD8 pathway as a new approach to enhance ATRA-induced differentiation of acute promyelocytic leukemia cells

et al. 2018

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The cullin-RING ligase (CRL)-NEDD8 pathway maintains essential cellular processes, including cell cycle progression, apoptosis, autophagy, DNA repair, antigen processing and signal transduction. Growing evidence demonstrates that the alteration of the CRL-NEDD8 pathway in some cancers constitutes an attractive target for therapeutic intervention, but the roles of CRL-NEDD8 pathway in acute promyelocytic leukemia (APL) is still unclear. In the present study, we found that ATRA could decrease the expression of NEDD8-activating enzyme E1 (NAE1) and inhibit the neddylation of cullin1 and cullin3 in the APL cell line NB4. Inactivation of cullin neddylation promoted self-degradation of F-box proteins (Skp2, KLHL20, βTrCP) and up-regulated the protein expression of p27kip, DEPTOR and DAPK1. MLN4924, a novel inhibitor of NAE1, significantly suppressed cell growth and enhanced apoptosis of APL cells by blocking cullin neddylation and subsequent accumulation of CRL E3 substrates. Furthermore, MLN4924 effectively enhanced ATRA-induced differentiation of APL cells by promoting autophagy. Our findings not only provide further insights into the mechanism of the CRL-NEDD8 axis, but also provide a better understanding of this pathway as a potential target for therapeutic intervention in APL.

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Rig-G negatively regulates SCF-E3 ligase activities by disrupting the assembly of COP9 signalosome complex

Cited by 10 publications

References 29 publications

The NEDD8 modification pathway in plants

The NEDD8 modification pathway in plants

Regulation of Cop9 signalosome activity by the EF-hand Ca2+-binding protein tescalcin

Inhibition of CRL-NEDD8 pathway as a new approach to enhance ATRA-induced differentiation of acute promyelocytic leukemia cells

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