Exclusion of germ plasm proteins from somatic lineages by cullin-dependent degradation

DeRenzo, Cynthia; Reese, Kimberly J.; Seydoux, Géraldine

doi:10.1038/nature01887

Cited by 171 publications

(217 citation statements)

References 28 publications

(2 reference statements)

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“…Thus, it seems highly likely that ELC‐1 affects the stability of a broader range of substrates than VHL‐1 does. Indeed, an ELC‐1‐containing E3 ligase that contains ZIF‐1 as a substrate‐specific subunit affects reproduction by destabilizing PIE‐1, an essential factor for germ line development (DeRenzo et al ., 2003). Thus, the reduced fertility caused by ELC‐1 may act through both the VHL‐1/HIF‐1 and ZIF‐1/PIE‐1 axes.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of elongin C promotes longevity and protein homeostasis via HIF‐1 in C. elegans

et al. 2015

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SummaryThe transcription factor hypoxia‐inducible factor 1 (HIF‐1) is crucial for responses to low oxygen and promotes longevity in Caenorhabditis elegans. We previously performed a genomewide RNA interference screen and identified many genes that act as potential negative regulators of HIF‐1. Here, we functionally characterized these genes and found several novel genes that affected lifespan. The worm ortholog of elongin C, elc‐1, encodes a subunit of E3 ligase and transcription elongation factor. We found that knockdown of elc‐1 prolonged lifespan and delayed paralysis caused by impaired protein homeostasis. We further showed that elc‐1 RNA interference increased lifespan and protein homeostasis by upregulating HIF‐1. The roles of elongin C and HIF‐1 are well conserved in eukaryotes. Thus, our study may provide insights into the aging regulatory pathway consisting of elongin C and HIF‐1 in complex metazoans.

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Section: Discussionmentioning

confidence: 99%

Inhibition of elongin C promotes longevity and protein homeostasis via HIF‐1 in C. elegans

et al. 2015

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“…Degradation of PIE-1 is guided by ZIF-1 binding to one of the two CCCH zinc fingers of PIE-1. Mutations in the first CCCH domain of PIE-1 or loss of ZIF-1 activity each disrupt active destruction of PIE-1 remaining in the somatic daughters (DeRenzo et al 2003).…”

Section: Resultsmentioning

confidence: 99%

“…PIE-1 degradation in the PGCs is abnormally delayed in emb-4 embryos: in the mutants, it eventually disappears by the 100-to 150-cell stage in contrast to the sudden disappearance near or at PGC birth in wild-type embryos. The zinc-finger-binding protein ZIF-1 has been shown to be essential for clearance of maternal germline factors, including PIE-1, from early somatic blastomeres (DeRenzo et al 2003). This process has been proposed to comprise a switch from oocyte/ germline characteristics to zygotic developmental control (DeRenzo et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…The zinc-finger-binding protein ZIF-1 has been shown to be essential for clearance of maternal germline factors, including PIE-1, from early somatic blastomeres (DeRenzo et al 2003). This process has been proposed to comprise a switch from oocyte/ germline characteristics to zygotic developmental control (DeRenzo et al 2003). Interestingly, we have shown that ZIF-1 is also required for timely PIE-1 degradation in the PGCs, which suggests that there is also a switch to the activation of zygotic processes in the germline that establish and/or maintain this lineage during embryonic development.…”

Section: Discussionmentioning

confidence: 99%

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emb-4Is a Conserved Gene Required for Efficient Germline-Specific Chromatin Remodeling DuringCaenorhabditis elegansEmbryogenesis

Checchi

Kelly

2006

Genetics

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In C. elegans, germline blastomeres are initially kept transcriptionally quiescent by the maternally loaded CCCH zinc-finger protein PIE-1. PIE-1 disappears upon the birth of the primordial germ cells Z2 and Z3, yet these cells appear to remain quiescent. We have previously demonstrated that there is a chromatin-based repression that succeeds PIE-1 degradation. The chromatin in Z2/Z3 loses certain histone modifications, including histone H3 lysine 4 dimethylation (H3K4me2), a conserved marker for transcriptionally competent chromatin. We find that mutations in the maternal-effect gene emb-4 cause defects in both PIE-1 degradation and germline-specific chromatin remodeling. emb-4 encodes a highly conserved protein with orthologs in fly, mouse, and human and has a subtle role in Notch signaling. The embryonic phenotype of emb-4 is consistent with a defect in the efficient and timely activation of developmental programs, including germline chromatin remodeling. We also find that, as in early somatic blastomeres, the degradation of PIE-1 in Z2/Z3 is facilitated by zinc-finger-interacting protein ZIF-1, and in the absence of either zif-1 or emb-4, PIE-1 is abnormally retained in Z2/Z3.

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“…b (Bai et al, 1996;Feldman et al, 1997;Skowyra et al, 1997Skowyra et al, , 1999Dealy et al, 1999;Kamura et al, 1999b;Kitagawa et al, 1999;Ohta et al, 1999;Seol et al, 1999;Tan et al, 1999;Ganoth et al, 2001;Strohmaier et al, 2001). c (Feng et al, 1999;Kamura et al, 2000;Epstein et al, 2001;Ivan et al, 2001;Jaakkola et al, 2001;Brower et al, 2002;DeRenzo et al, 2003; CCCH ¼ a class of zinc-finger proteins). d (Singer et al, 1999;Zhou et al, 2001;Kurz et al, 2002;Ou et al, 2002;Furukawa et al, 2003;Geyer et al, 2003;Pintard et al, 2003b;Xu et al, 2003).…”

Section: Cullinsmentioning

confidence: 99%

Nedd8 on cullin: building an expressway to protein destruction

et al. 2004

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This review summarizes recent advances concerning the Nedd8 regulatory pathway in four areas. One, substantial progress has been made in delineating the role of cullin family proteins, the only known substrates of the Nedd8 modification system. Cullins are molecular scaffolds responsible for assembling the ROC1/Rbx1 RING-based E3 ubiquitin ligases, of which several play a direct role in tumorigenesis. Two, a large body of work has helped elucidate the molecular details underlying the Nedd8 modification reaction, which results in covalent conjugation of a Nedd8 moiety onto a conserved cullin lysine residue. Three, studies using a variety of genetic model systems have established an essential role for Nedd8 in cell cycle control and in embryogenesis by upregulating the activities of cullin-based E3 ligases. In vitro experiments have revealed a direct role for Nedd8 in activating ubiquitination. Construction of a model of the ROC1/ Rbx1-CUL1-Nedd8 structure suggests a mechanism by which the cullin-linked Nedd8 may assist the neighboring ROC1/Rbx1 in landing and positioning the E2 conjugating enzyme for the ubiquitin transfer reaction. Finally, increasing evidence indicates that removal of Nedd8 from its cullin targets, by the action of COP9 Signalosome and possibly other proteases, plays a significant role in the regulation of cullin-mediated proteolysis.

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Exclusion of germ plasm proteins from somatic lineages by cullin-dependent degradation

Cited by 171 publications

References 28 publications

Inhibition of elongin C promotes longevity and protein homeostasis via HIF‐1 in C. elegans

Inhibition of elongin C promotes longevity and protein homeostasis via HIF‐1 in C. elegans

emb-4Is a Conserved Gene Required for Efficient Germline-Specific Chromatin Remodeling DuringCaenorhabditis elegansEmbryogenesis

Nedd8 on cullin: building an expressway to protein destruction

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