Degrade to create: developmental requirements for ubiquitin-mediated proteolysis during early<i>C. elegans</i>embryogenesis

Bowerman, Bruce; Kurz, Thimo

doi:10.1242/dev.02276

Cited by 70 publications

(61 citation statements)

References 105 publications

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“…Proteasome-mediated regulation of a developmental decision: The degradation of proteins by the proteasome is increasingly being realized as an important means of regulating many cellular processes and developmental decisions (Groll et al 2005;Bowerman and Kurz 2006;Naujokat and Saric 2007). Indeed, the proteasome is involved in regulating so many fundamental processes, such as the cell cycle (Glotzer et al 1991;Hershko et al 1991), that it is sometimes difficult to tease apart specific functions.…”

Section: Discussionmentioning

confidence: 99%

Proteasomal Regulation of the Proliferation vs. Meiotic Entry Decision in the Caenorhabditis elegans Germ Line

2008

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Reproductive fitness in many animals relies upon a tight balance between the number of cells that proliferate in the germ line and the number of cells that enter meiosis and differentiate as gametes. In the Caenorhabditis elegans germ line, the GLP-1/Notch signaling pathway controls this balance between proliferation and meiotic entry. Here we describe the identification of the proteasome as an additional regulator of this balance. We show that a decrease in proteasome activity, through either genetic mutation or RNAi to core components of the proteasome, shifts this balance toward excess germ-line proliferation. We further demonstrate that there are likely two or more proteasome targets that contribute to excess germ-line proliferation when proteasome activity is reduced. One of these targets is likely a component or regulator of the Notch-signaling pathway, while the other functions on one of the two major redundant genetic pathways downstream of GLP-1/Notch signaling. We propose a model in which the proteasome degrades proteins that are necessary for proliferation as cells switch from proliferation to meiotic entry.

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Section: Discussionmentioning

confidence: 99%

Proteasomal Regulation of the Proliferation vs. Meiotic Entry Decision in the Caenorhabditis elegans Germ Line

2008

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“…SREBP-2 is degraded via the ubiquitin-proteosome pathway after its phosphorylation and ubiquination [50][51][52]. Though the ubiquitin-proteosome system for degradation is active during development [53,54], it seems that the SREBPs would not be readily modified and/or degraded during this time of rapid growth since sterol synthesis rates remain relatively active in the presence of cholesterol. Lack of SREBP-2 degradation may be the result of a change in proteosome activity [55] or rate of de-ubiquitination [41].…”

Section: Srebp-2 Degradationmentioning

confidence: 99%

Inability to fully suppress sterol synthesis rates with exogenous sterol in embryonic and extraembyronic fetal tissues

Yao

Jenkins

Horn

et al. 2007

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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SUMMARYThe requirement for cholesterol is greater in developing tissues (fetus, placenta, and yolk sac) as compared to adult tissues. Here, we compared cholesterol-induced suppression of sterol synthesis rates in the adult liver to the fetal liver, fetal body, placenta, and yolk sac of the Golden Syrian hamster. Sterol synthesis rates were suppressed maximally in non-pregnant adult livers when cholesterol concentrations were increased. In contrast, sterol synthesis rates were suppressed only marginally in fetal livers, fetal bodies, placentas, and yolk sacs when cholesterol concentrations were increased. To begin to elucidate the mechanism responsible for the blunted response of sterol synthesis rates in fetal tissues to exogenous cholesterol, the ratio of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) to Insig-1 was measured in these same tissues since the ratio of SCAP to the Insigs can impact SREBP processing. The fetal tissues had anywhere from a 2-to 6-fold greater ratio of SCAP to Insig-1 than did the adult liver, suggesting constitutive processing of the SREBPs. As expected, the level of mature, nuclear SREBP-2 was not different in the fetal tissues with different levels of cholesterol whereas it was different in adult livers. These findings indicate that the suppression of sterol synthesis to exogenous sterol is blunted in developing tissues and the lack of response appears to be mediated at least partly through relative levels of Insigs and SCAP.

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“…In contrast, C. elegans CUL-2 is required for progression through meiosis and for the localized degradation of cell fate determinants in one-cell-stage embryos (Liu et al 2004;Sonneville and Gonczy 2004), but neddylationdefective mutants do not exhibit these early defects (Bowerman and Kurz 2006). Cullin neddylation is mediated by the Nedd8 protein conjugation pathway, which begins with a heterodimeric E1-activating enzyme consisting of ULA-1 and RFL-1 (Uba3p in budding yeast) and also includes the E2-conjugating enzyme UBC-12 ( Jones and Candido 2000;Srayko et al 2000;Kurz et al 2002) and the E3 ligase DCN-1 (Kurz et al 2005).…”

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confidence: 94%

“…In the early Caenorhabditis elegans embryo, these include oocyte maturation, cell cycle progression, cell polarization, and cell fate patterning, all of which require the timely destruction of maternally expressed proteins (Bowerman and Kurz 2006;Greenstein and Lee 2006). One C. elegans protein targeted for proteolysis early in embryogenesis is MEI-1, the AAA-ATPase subunit of the microtubule-severing complex called katanin (Mains et al 1990;Dow and Mains 1998;Srayko et al 2000;Kurz et al 2002;Pintard et al 2003a;Xu et al 2003).…”

mentioning

confidence: 99%

“…CUL-3 is the only C. elegans Cullin thus far identified that requires modification by the ubiquitin-like protein Nedd8 (Bowerman and Kurz 2006). In contrast, C. elegans CUL-2 is required for progression through meiosis and for the localized degradation of cell fate determinants in one-cell-stage embryos (Liu et al 2004;Sonneville and Gonczy 2004), but neddylationdefective mutants do not exhibit these early defects (Bowerman and Kurz 2006).…”

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confidence: 99%

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Using RNA Interference to Identify Specific Modifiers of a Temperature-Sensitive, Embryonic-Lethal Mutation in the Caenorhabditis elegans Ubiquitin-Like Nedd8 Protein Modification Pathway E1-Activating Gene rfl-1

Dorfman

Gomes²,

O’Rourke³

et al. 2009

Genetics

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The essential Caenorhabditis elegans gene rfl-1 encodes one subunit of a heterodimeric E1-activating enzyme in the Nedd8 ubiquitin-like protein conjugation pathway. This pathway modifies the Cullin scaffolds of E3 ubiquitin ligases with a single Nedd8 moiety to promote ligase function. To identify genes that influence neddylation, we used a synthetic screen to identify genes that, when depleted with RNAi, enhance or suppress the embryonic lethality caused by or198ts, a temperature-sensitive (ts) mutation in rfl-1. We identified reproducible suppressor and enhancer genes and employed a systematic specificity analysis for each modifier using four unrelated ts embryonic lethal mutants. Results of this analysis highlight the importance of specificity controls in identifying genetic interactions relevant to a particular biological process because 8/14 enhancers and 7/21 suppressors modified lethality in other mutants. Depletion of the strongest specific suppressors rescued the early embryonic cell division defects in rfl-1(or198ts) mutants. RNAi knockdown of some specific suppressors partially restored Cullin neddylation in rfl-1(or198ts) mutants, consistent with their gene products normally opposing neddylation, and GFP fusions to several suppressors were detected in the cytoplasm or the nucleus, similar in pattern to Nedd8 conjugation pathway components in early embryonic cells. In contrast, depletion of the two strongest specific enhancers did not affect the early embryonic cell division defects observed in rfl-1(or198ts) mutants, suggesting that they may act at later times in other essential processes. Many of the specific modifiers are conserved in other organisms, and most are nonessential. Thus, when controlled properly for specificity, modifier screens using conditionally lethal C. elegans mutants can identify roles for nonessential but conserved genes in essential processes.

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Degrade to create: developmental requirements for ubiquitin-mediated proteolysis during earlyC. elegansembryogenesis

Cited by 70 publications

References 105 publications

Proteasomal Regulation of the Proliferation vs. Meiotic Entry Decision in the Caenorhabditis elegans Germ Line

Proteasomal Regulation of the Proliferation vs. Meiotic Entry Decision in the Caenorhabditis elegans Germ Line

Inability to fully suppress sterol synthesis rates with exogenous sterol in embryonic and extraembyronic fetal tissues

Using RNA Interference to Identify Specific Modifiers of a Temperature-Sensitive, Embryonic-Lethal Mutation in the Caenorhabditis elegans Ubiquitin-Like Nedd8 Protein Modification Pathway E1-Activating Gene rfl-1

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