Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis

Nishitani, Hideo; Sugimoto, Nozomi; Roukos, Vassilis; Nakanishi, Yohsuke; Saijo, Masafumi; Obuse, Chikashi; Tsurimoto, Toshiki; Nakayama, Keiichi I.; Nakayama, Keiko; Fujita, Masatoshi; Lygerou, Zoi; Nishimoto, Tetsuya

doi:10.1038/sj.emboj.7601002

Cited by 355 publications

(548 citation statements)

References 51 publications

(92 reference statements)

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“…DDB1 in particular is involved in many distinct DNA response and DNA repair pathways. For example, DDB1 binds to SKP2 and plays a role in the ubiquitination of CDKN1B, a cyclin-dependent kinase inhibitor (Nishitani et al 2006) and may recruit nucleotide excision repair proteins in order to repair DNA damage (Li et al 2006). Deficiency in DDB1 is associated with xeroderma pigmentosum (Kapetanaki et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Accelerated protein evolution analysis reveals genes and pathways associated with the evolution of mammalian longevity

Magalhães

2011

AGE

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The genetic basis of the large species differences in longevity and aging remains a mystery. Thanks to recent large-scale genome sequencing efforts, the genomes of multiple species have been sequenced and can be used for cross-species comparisons to study species divergence in longevity. By analyzing proteins under accelerated evolution in several mammalian lineages where maximum lifespan increased, we identified genes and processes that are candidate targets of selection when longevity evolves. We identified several proteins with longevity-specific selection patterns, including COL3A1 that has previously been related to aging and proteins related to DNA damage repair and response such as DDB1 and CAPNS1. Moreover, we found that processes such as lipid metabolism and cholesterol catabolism show such patterns of selection and suggest a link between the evolution of lipid metabolism, cholesterol catabolism, and the evolution of longevity. Lastly, we found evidence that the proteasome-ubiquitin system is under selection specific to lineages where longevity increased and suggest that its selection had a role in the evolution of longevity. These results provide evidence that natural selection acts on species when longevity evolves, give insights into adaptive genetic changes associated with the evolution of longevity in mammals, and provide evidence that at least some repair systems are selected for when longevity increases.

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Section: Discussionmentioning

confidence: 99%

Accelerated protein evolution analysis reveals genes and pathways associated with the evolution of mammalian longevity

Magalhães

2011

AGE

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“…8 Although by a still elusive mechanism, the rapid and dose-dependent degradation of c-MYC in cells after UV-irradiation that we report here is reminiscent of the UV-induced degradation of the replication licencing factor Cdt1 that requires the presence of L2DTL, PCNA and the DDB1/CUL4 E3 ligase complexes. [60][61][62] It has been shown that c-MYC overexpression antagonizes the p53-dependent cell cycle arrest following DNA damage. 63,64 Consequently, an excess of c-MYC promotes chromosomal instability probably by combined effects since it increases DNA damage and it overcomes cell cycle arrest.…”

Section: Discussionmentioning

confidence: 99%

“…The wild-type, ΔMBI (aa [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63] and ΔMBII (aa 129-143) N-terminally FLAG tagged c-MYC2 coding pcDNA3 plasmids were kindly provided by Dr B. Lüscher (Institut für Biochemie, Aachen, Germany). ΔMBIII (aa 129-143), ΔA (aa 1-63), ΔB (aa 64-126), ΔC (aa 127-189), ΔD (aa 190-252), ΔE (aa 253-315), ΔF (aa 316-378), ΔG (aa 379-439), ΔCT (aa 354-439), T58A S62A and T358A S373A T400A deletions and point mutations were done by PCR.…”

Section: Methodsmentioning

confidence: 99%

c-Myc protein is degraded in response to UV irradiation

Britton¹,

Salles²,

Calsou³

2008

Cell Cycle

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The c-MYC proto-oncogene encodes a transcription factor that is critical for cell growth and proliferation. It is one of the genes frequently altered in cancer cells in which it exhibits constitutive activity. The half-life of c-MYC is very short in quiescent cells due to ubiquitin-mediated proteolysis. We report here the rapid and dose-dependent decline of c-MYC protein level after UV-irradiation in various human and rodent cells. This decline is due to a proteasomal degradation of c-MYC protein and does not require the binding sites for the FBW7 and SKP2 ubiquitin ligases. Together, our data exclude a prominent role for the stress-responsive kinase PAK2, for the major phosphoinositide 3-kinase related protein kinases ATR, ATM, DNA-PK and mTOR and for ERK, JNK and p38 mitogen activated protein kinases in this UV-induced degradation process. We propose that c-MYC degradation is part of the global cell response to UV-damage, complementary to the accumulation and activation of the p53 transcription factor. By contributing to the replication arrest after infliction of lesions to the genome, the induced degradation of c-MYC may be part of the safeguard mechanisms maintaining genome stability.

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“…In addition, cotransfected Geminin increased the expression of both WT and DPEST Cdt1 (Fig. 3b), indicating that by blocking origin licensing and S-phase entry Geminin indirectly inhibited DNA synthesiscoupled degradation 13 of both Cdt1 variants. Finally, coimmunoprecipitation experiments indicated that the PEST deletions did not affect the Cdt1-Geminin interaction (Fig.…”

Section: Resultsmentioning

confidence: 99%

A spontaneous Cdt1 mutation in 129 mouse strains reveals a regulatory domain restraining replication licensing

et al. 2013

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Cdt1 is required for loading the replicative DNA helicase MCM2/7, a process known as DNA replication licensing. Here we show that 129 mouse strains express a Cdt1 mutated allele with enhanced licensing activity. The mutation, named D 6 PEST, involves a six-amino acid deletion within a previously uncharacterized PEST-like domain. Cdt1 D 6 PEST and more extensive deletions exhibit increased re-replication and transformation activities that are independent of the Geminin and E3 ligase pathways. This PEST domain negatively regulates cell cycledependent chromatin recruitment of Cdt1 in G2/M phases of the cell cycle. Mass spectrometry analysis indicates that Cdt1 is phosphorylated at sites within the deleted PEST domain during mitosis. This study reveals a conserved new regulatory Cdt1 domain crucial for proper DNA licensing activity and suggests a mechanism by which the presence of Cdt1 in G2/M phases does not lead to premature origin licensing. These results also question the usage of 129 mouse strains for knockout analyses.

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Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis

Cited by 355 publications

References 51 publications

Accelerated protein evolution analysis reveals genes and pathways associated with the evolution of mammalian longevity

Accelerated protein evolution analysis reveals genes and pathways associated with the evolution of mammalian longevity

c-Myc protein is degraded in response to UV irradiation

A spontaneous Cdt1 mutation in 129 mouse strains reveals a regulatory domain restraining replication licensing

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