<i>Schizosaccharomyces pombe</i> Ddb1 Recruits Substrate-Specific Adaptor Proteins through a Novel Protein Motif, the DDB-Box

Fukumoto, Yasunori; Dohmae, Naoshi; Hanaoka, Fumio

doi:10.1128/mcb.00757-08

Cited by 18 publications

(16 citation statements)

References 46 publications

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“…(3) Additional residues besides the Arg are required for binding with DDB1. For example, a 6-amino acid sequence in the DWD/DCAF/CDW protein WDR21 which lies outside the WD40 repeats is important for binding with DDB1 [45]. This region was identified by sequence homology in some, but not all, DWD/DCAF/CDW proteins.…”

Section: Dwd/dcaf/cdw Proteins: the Substrate Receptorsmentioning

confidence: 99%

CRL4s: the CUL4-RING E3 ubiquitin ligases

Jackson

Xiong

2009

Trends in Biochemical Sciences

355

365

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The evolutionarily conserved cullin family proteins can assemble as many as 400 distinct E3 ubiquitin ligase complexes that regulate diverse cellular pathways. CUL4, one of three founding cullins conserved from yeast to humans, uses a large β-propeller protein, DDB1, as a linker to interact with a subset of WD40 proteins that serve as substrate receptors, forming as many as 90 E3 complexes in mammals. Many CRL4 complexes are involved in chromatin regulation and are frequently hijacked by different viruses. Cullins: the scaffoldThe ubiquitin pathway regulates a wide range of diverse cellular processes by covalently attaching ubiquitin to specific substrate proteins either to alter their functions nonproteolytically or more commonly to promote their degradation by the 26S proteosome [1]. Ubiquitylation begins with the ATP dependent activation of ubiquitin by the E1 enzyme, and is followed by the subsequent transfer of ubiquitin to an E2 ubiquitin conjugating enzyme, and finally an E3 ubiquitin ligase is responsible for recognizing a specific substrate and promoting ubiquitin ligation. Over a thousand distinct E3 ligases, belonging to two major families, the HECT family and the RING family, are present in higher eukaryotes. Human cells contain as many as 28 HECT proteins and most, if not all, are believed to function as E3 ligases. More than 450 RING proteins are expressed in human cells and E3 ligase activity has been experimentally demonstrated for many of them.Although not containing a RING domain themselves, members of the evolutionarily conserved cullin family can bind with a small RING protein, either ROC1 or ROC2 (for RING of Cullins; also known as Rbx and Hrt1), to constitute a large family of cullin-RING E3 ligases (CRLs). There are three cullins in yeast, six in Caenorhabditis elegans and Drosophila melanogaster (CUL1-6), up to nine in Arabidopsis thaliana, and six in humans (CUL1, 2, 3, 4A, 4B and 5). In addition, three other proteins, CUL7 and CUL9 (also known as PARC) in mammals and APC2 (anaphase promoting complex subunit 2) in all eukaryotes, contain significant sequence homology to cullins over a ~180 residue region and bind ROC or a homologous small RING protein, APC11. Unlike other RING E3 ligases, cullins do not bind substrates directly, but rather rely on substrate recruiting receptors that are typically joined to the cullin complex by a linker protein (Fig. 1). Remarkably, each cullin can associate with a different family of substrate receptors, leading to the assembly of as many as 400 distinct CRLs. A recent estimate suggests that 20% of all proteins subject to proteasomal degradation are targeted by CRLs [2].Corresponding author: Xiong, Y. (yxiong@email.unc.edu). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable ...

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Section: Dwd/dcaf/cdw Proteins: the Substrate Receptorsmentioning

confidence: 99%

CRL4s: the CUL4-RING E3 ubiquitin ligases

Jackson

Xiong

2009

Trends in Biochemical Sciences

355

365

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“…CUL4A and CUL4B use an overlapping set of DCAF proteins and exhibit partially redundant functions, but they may also associate with distinct substrate-adaptors for specific cellular functions. The topology of the CRL4 complex is also conserved in fission yeast [33,34] and in budding yeast [35]. Substrate-recognition subunits represent large families of proteins such that the potential number of CRLs is staggering with more than 500 hundred members.…”

Section: Composition Of Crl Complexesmentioning

confidence: 99%

Regulation of cullin-RING E3 ubiquitin-ligases by neddylation and dimerization

Merlet

Burger

Gomes

et al. 2009

Cell. Mol. Life Sci.

172

174

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Cullin-RING E3 ubiquitin-Ligases (CRLs) are the most prominent class of ubiquitin-ligases. By controlling the stability of a cohort of key regulators, CRLs impinge on many cellular and biological processes such as immunity, development, transcription, cell signalling and cell cycle progression. CRLs are multi-subunit complexes composed of a catalytic site and a substrate recognition module nucleated around a cullin scaffold protein. Most eukaryotic genomes encode at least five distinct cullins, and each of these cullins recruits a specific substrate-recognition module such that CRL complexes are modular. Despite their considerable diversity, CRLs are regulated by similar mechanisms. In particular, recent observations indicate that conformational variability induced by CRL dimerization and by conjugation of the ubiquitin-like protein NEDD8 on the cullin subunit stimulates substrate polyubiquitination. In this review, we discuss the composition of CRL complexes and the various molecular mechanisms controlling their activity.

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“…One hour before adding Adriamycin or after the end of Adriamycin exposure, 5 M SU6656, 20 M PP2, or 100 ng/ml BI2536 was added to the culture medium and included until the end of the culture period. Cells were solubilized in SDS-PAGE sample buffer by boiling and sonication or lysed in high salt buffer (50 mM HEPES-NaOH (pH 7.8), 300 mM KCl, 1% Triton X-100, 20% glycerol, and inhibitors of proteases and phosphatases) (59). The intensity of each protein band was quantitated using a ChemiDoc XRS-Plus image analyzer (Bio-Rad) and calculated as -fold increase Ϯ standard deviation (S.D.)…”

Section: Methodsmentioning

confidence: 99%

Src Family Kinases Promote Silencing of ATR-Chk1 Signaling in Termination of DNA Damage Checkpoint

Fukumoto

Morii

Miura

et al. 2014

Journal of Biological Chemistry

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Background: Once DNA repair is completed, the DNA damage checkpoint is terminated, and the cell cycle is resumed. Results: Src inhibition induced a delay in G 2 checkpoint recovery and persistent ATR-Chk1 activation. Conclusion: Src inhibits ATR signaling to promote recovery from G 2 checkpoint arrest. Significance: Src sends a termination signal between the completion of DNA repair and the initiation of checkpoint termination.

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Schizosaccharomyces pombe Ddb1 Recruits Substrate-Specific Adaptor Proteins through a Novel Protein Motif, the DDB-Box

Cited by 18 publications

References 46 publications

CRL4s: the CUL4-RING E3 ubiquitin ligases

CRL4s: the CUL4-RING E3 ubiquitin ligases

Regulation of cullin-RING E3 ubiquitin-ligases by neddylation and dimerization

Src Family Kinases Promote Silencing of ATR-Chk1 Signaling in Termination of DNA Damage Checkpoint

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