| Symbol: {Name}{Links}
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Flybase ID: {Flybase_ID} |
| Synonyms: {Name}
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{GadFly} |
| Function: {Short_Function} |
{LocusLink} |
| Keywords: {Keywords} |
{Interactive_Fly} |
- ubiquitin-like small protein modifier
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- The Nedd8 conjugation process, called neddylation, is similar to ubiquitination.
- Neddylation utilizes the E1 activating-enzyme complex composed of
two subunits, APP-BP1 and UBA3, and the E2 conjugating-enzyme, UBC12
(Yeh et al. 2000).
- The SCF complex consists of core subunits: Cul1/Cdc53,
Skp1, Roc1/Hrt/Rbx1, and a substrate-recognition F-box protein. Cul1
functions as a scaffold protein within the SCF complex; the N-terminal
domain of Cul1 interacts with the adaptor protein Skp1 that links with
the F-box protein, and the C terminal domain interacts with Roc1 and
the ubiquitin E2 enzyme. In vitro, neddylation of Cul1 is required for
ubiquitination of IB and p27Kip1 (Morimoto et al. 2000; Podust et
al. 2000; Read et al. 2000). In addition, neddylation enhances E2-ubiquitin
recruitment to SCF (Kawakami et al. 2001). In fission yeast, Nedd8 is
essential for the SCFmediated degradation of Rum-1, a cyclin-dependent
kinase inhibitor (Osaka et al. 2000). In Arabidopsis thaliana, the Nedd8
pathway is required for SCF-mediated Auxin response (Pozo et al. 1998;
Schwechheimer et al. 2001). In mice deficient for UBA3, a subunit of
the E1 enzyme in neddylation, embryonic development is aberrant, with
accumulation of two putative SCF substrates, -catenin and cyclin E
(CycE; Tateishi et al. 2001). In the SCF complex, F-box proteins convey
substrate specificity by direct interaction with substrates for degradation.
Many F-box proteins have been characterized in metazoans, and increasing
numbers of specific targets for F-box proteins are being found (Deshaies
1999). Among them, the Drosophila F-box protein Slimb and its mammalian
homolog -TrCP are well characterized for their target specificity (for
review, see Maniatis 1999). The specific targets for Slimb/-TrCP are
pIB in the Dorsal/NFB pathway, Arm/-catenin in the Wg/Wnt pathway,
and Ci/Gli in the Hedgehog (Hh) pathway (Jiang and Struhl 1998; Yaron
et al. 1998; Spencer et al. 1999; Winston et al. 1999)
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- The only known substrates of neddylation are Cullin family proteins,Cul1,
Cul2, Cul3, Cul4A, Cul4B,and Cul5, which have been shown to be modified
by Nedd8 in mammalian cells (Osaka et al. 1998; Hori et al. 1999).
- Cullins directly interact with Roc1, a Ring finger protein, and the
Cullin-Roc1 complex comprises the core module of a series of ubiquitin
E3 ligases, which confer substrate specificity and therefore regulate
the degradation process (Kamura et al. 1999b; Ohta et al. 1999; Seol
et al. 1999; Skowyra et al. 1999).
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- highly conserved from yeast to mammals
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- null mutants were growth-arrested in the first-instar larval stage
and died within several days without further growth (Fig. 1B). (Ou,
2002)
- mutant clones in wing sics accumulated high levels of full-length
Ci and Arm proteins and accumulated CycE in wing discs (Ou,
2002)
- Embryos laid by Nedd8AN015/Nedd8203 females in which Nedd8203 is a
hypomorphic allele, the twist expression domain was reduced along the
dorsoventral axis and often found missing in many cells (Fig. 1Q), revealing
a requirement for Nedd8 in Dorsal signaling. (Ou,
2002)
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