E3 ubiquitin ligases and mitosis: embracing the complexity

Sumara, Izabela; Maerki, Sarah; Peter, Matthias

doi:10.1016/j.tcb.2007.12.001

Cited by 44 publications

(37 citation statements)

References 99 publications

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“…4C). To obtain a more comprehensive picture of APC/C target regulation by C/EBPδ, we also analyzed expression of other APC/C substrates (26). C/EBPδ expression in MCF-7 cells down-regulated Skp2 and Plk-1 along with cyclin D1.…”

Section: C/ebpδ Regulates Genome Integrity Through Modulation Of Cyclmentioning

confidence: 99%

C/EBPδ targets cyclin D1 for proteasome-mediated degradation via induction of CDC27/APC3 expression

Pawar

Sarkar

Balamurugan

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The transcription factor CCAAT/enhancer binding protein δ (C/EBPδ, CEBPD, NFIL-6β) has tumor suppressor function; however, the molecular mechanism(s) by which C/EBPδ exerts its effect are largely unknown. Here, we report that C/EBPδ induces expression of the Cdc27 (APC3) subunit of the anaphase promoting complex/cyclosome (APC/C), which results in the polyubiquitination and degradation of the prooncogenic cell cycle regulator cyclin D1, and also down-regulates cyclin B1, Skp2, and Plk-1. In C/EBPδ knockout mouse embryo fibroblasts (MEF) Cdc27 levels were reduced, whereas cyclin D1 levels were increased even in the presence of activated GSK-3β. Silencing of C/EBPδ, Cdc27, or the APC/C coactivator Cdh1 (FZR1) in MCF-10A breast epithelial cells increased cyclin D1 protein expression. Like C/EBPδ, and in contrast to cyclin D1, Cdc27 was down-regulated in several breast cancer cell lines, suggesting that Cdc27 itself may be a tumor suppressor. Cyclin D1 is a known substrate of polyubiquitination complex SKP1/CUL1/F-box (SCF), and our studies show that Cdc27 directs cyclin D1 to alternative degradation by APC/C. These findings shed light on the role and regulation of APC/C, which is critical for most cellular processes.

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Section: C/ebpδ Regulates Genome Integrity Through Modulation Of Cyclmentioning

confidence: 99%

C/EBPδ targets cyclin D1 for proteasome-mediated degradation via induction of CDC27/APC3 expression

Pawar

Sarkar

Balamurugan

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…It has previously been shown that this can be mediated by interaction between substrate proteins and BTB domain-containing subunits of the ubiquitin ligase complexes (Bosu and Kipreos 2008;Hotton and Callis 2008;Petroski and Deshaies 2005;Sumara et al 2008). However, our results indicate that recruitment can also occur by interaction between PEST sequences in a substrate protein, in this case HSF2, and the Cul3 subunit of the Cul3-RING ligase complexes.…”

Section: Discussionmentioning

confidence: 99%

“…Cul3, a member of the Cullin family of proteins, is a subunit of a Cullin-RING ubiquitin E3 ligase complex that polyubiquitinates many important proteins, leading to their degradation by the proteasome (Bosu and Kipreos 2008;Hotton and Callis 2008;Petroski and Deshaies 2005;Sumara et al 2008). Cul3-containing ubiquitin ligases have been found to play important roles in the regulation of mitosis, development, cytoskeletal proteins, and transcription factors (Pintard et al 2004;Sumara et al 2008;.…”

Section: Introductionmentioning

confidence: 99%

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PEST sequences mediate heat shock factor 2 turnover by interacting with the Cul3 subunit of the Cul3-RING ubiquitin ligase

Xing

Hong

Sarge

2010

Cell Stress and Chaperones

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Cullin-RING ubiquitin ligases promote the polyubiquitination and degradation of many important cellular proteins, which previous studies indicated can be targeted for degradation via interaction with BTB domaincontaining subunits of this E3 ligase complex. PEST domains are known to promote the degradation of proteins that contain them. However, the molecular mechanism by which PEST sequences promote degradation of these proteins is not understood. Here we show that the PEST sequences of a short-lived protein called HSF2 interact with Cullin3, a subunit of a Cullin-RING E3 ubiquitin ligase, and that this interaction mediates the Cul3-dependent ubiquitination and degradation of HSF2. These results indicate how, at the molecular level, PEST sequences can promote the proteolysis of proteins that contain them. They also expand understanding of the mechanisms by which substrates can be recruited to Cullin-RING E3 ubiquitin ligases to include interactions between PEST sequences and Cul3.

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“…The first mitotic spindle differs from its meiotic counterpart in size, morphology, and intracellular location and likely requires the labeling of meiosis-specific proteins for degradation to prevent their interference with subsequent mitotic divisions (Lu and Mains, 2007). Recent studies in mammalian cells and in Caenorhabditis elegans have shown that multisubunit Cullin 3 (CUL3)-based E3 ligases are involved in regulating mitotic progression, cytokinesis, and the proper regulation of MT dynamics and spindle assembly during the meiosis-to-mitosis transition (Bowerman and Kurz, 2006;Sawin and Tran, 2006;Sumara et al, 2008). BTB (for Bric-à-Brac/Tramtrack/Broad complex) domain proteins appear to function in this complex as substrate-specific adaptors.…”

Section: Introductionmentioning

confidence: 99%

Germline-Specific MATH-BTB Substrate Adaptor MAB1 Regulates Spindle Length and Nuclei Identity in Maize

et al. 2012

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Germline and early embryo development constitute ideal model systems to study the establishment of polarity, cell identity, and asymmetric cell divisions (ACDs) in plants. We describe here the function of the MATH-BTB domain protein MAB1 that is exclusively expressed in the germ lineages and the zygote of maize (Zea mays). mab1 (RNA interference [RNAi]) mutant plants display chromosome segregation defects and short spindles during meiosis that cause insufficient separation and migration of nuclei. After the meiosis-to-mitosis transition, two attached nuclei of similar identity are formed in mab1 (RNAi) mutants leading to an arrest of further germline development. Transient expression studies of MAB1 in tobacco (Nicotiana tabacum) Bright Yellow-2 cells revealed a cell cycle-dependent nuclear localization pattern but no direct colocalization with the spindle apparatus. MAB1 is able to form homodimers and interacts with the E3 ubiquitin ligase component Cullin 3a (CUL3a) in the cytoplasm, likely as a substrate-specific adapter protein. The microtubule-severing subunit p60 of katanin was identified as a candidate substrate for MAB1, suggesting that MAB1 resembles the animal key ACD regulator Maternal Effect Lethal 26 (MEL-26). In summary, our findings provide further evidence for the importance of posttranslational regulation for asymmetric divisions and germline progression in plants and identified an unstable key protein that seems to be involved in regulating the stability of a spindle apparatus regulator(s).

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E3 ubiquitin ligases and mitosis: embracing the complexity

Cited by 44 publications

References 99 publications

C/EBPδ targets cyclin D1 for proteasome-mediated degradation via induction of CDC27/APC3 expression

C/EBPδ targets cyclin D1 for proteasome-mediated degradation via induction of CDC27/APC3 expression

PEST sequences mediate heat shock factor 2 turnover by interacting with the Cul3 subunit of the Cul3-RING ubiquitin ligase

Germline-Specific MATH-BTB Substrate Adaptor MAB1 Regulates Spindle Length and Nuclei Identity in Maize

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