Ubxd1 is a novel co-factor of the human p97 ATPase

Madsen, Lone Galmstrup; Andersen, Karen; Prag, Søren; Moos, Torben; Semple, Colin A.; Seeger, Michael; Hartmann‐Petersen, Rasmus

doi:10.1016/j.biocel.2008.06.008

Cited by 42 publications

(50 citation statements)

References 55 publications

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“…The C terminus of mouse Cdc48 homolog p97 (with the sequence TEDNDDDLYG-COOH) also interacts with the PUB domain (15,26). Even though the mouse PUB and PUL domains interact with Cdc48/ p97 with similar affinities, it seems that the mode of interaction is different.…”

Section: Comparison Of the Pul Domain Of Ufd3 With Other Proteins Conmentioning

confidence: 94%

“…With the identification of an Armadillo repeat as the Cdc48-binding site in Ufd3, there are now two known distinct domain architectures that interact with the C terminus of Cdc48, namely, the Armadillo motif as demonstrated here and the PUB domain present in mammalian PNGase and other proteins (15,26). Therefore, the ubiquitin mediated protein degradation pathway could be regulated by a complex protein interaction network, involving cooperative and/or competitive binding of various substrate processing cofactors, including Ufd2, Ufd3, and the PUB domain-containing proteins.…”

Section: Comparison Of the Pul Domain Of Ufd3 With Other Proteins Conmentioning

confidence: 99%

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An Armadillo motif in Ufd3 interacts with Cdc48 and is involved in ubiquitin homeostasis and protein degradation

Zhao

Schindelin

et al. 2009

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

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The yeast AAA-ATPase Cdc48 and the ubiquitin fusion degradation (UFD) proteins play important, evolutionarily conserved roles in ubiquitin dependent protein degradation. The N-terminal domain of Cdc48 interacts with substrate-recruiting cofactors, whereas the C terminus of Cdc48 binds to proteins such as Ufd3 that process substrates. Ufd3 is essential for efficient protein degradation and for maintaining cellular ubiquitin levels. This protein contains an N-terminal WD40 domain, a central ubiquitin-binding domain, and a C-terminal Cdc48-binding PUL domain. The crystal structure of the PUL domain reveals an Armadillo repeat with high structural similarity to importin-␣, and the Cdc48-binding site could be mapped to the concave surface of the PUL domain by biochemical studies. Alterations of the Cdc48 binding site of Ufd3 by sitedirected mutagenesis resulted in a depletion of cellular ubiquitin pools and reduced activity of the ubiquitin fusion degradation pathway. Therefore, our data provide direct evidence that the functions of Ufd3 in ubiquitin homeostasis and protein degradation depend on its interaction with the C terminus of Cdc48.

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Section: Comparison Of the Pul Domain Of Ufd3 With Other Proteins Conmentioning

confidence: 94%

Section: Comparison Of the Pul Domain Of Ufd3 With Other Proteins Conmentioning

confidence: 99%

An Armadillo motif in Ufd3 interacts with Cdc48 and is involved in ubiquitin homeostasis and protein degradation

Zhao

Schindelin

et al. 2009

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

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“…Fluorescence Microscopy-The localization of green fluorescent protein-tagged Txnl1 was determined in HeLa cells transiently transfected with pcDNA-DEST53-Txnl1, as described (26).…”

Section: Methodsmentioning

confidence: 99%

Thioredoxin Txnl1/TRP32 Is a Redox-active Cofactor of the 26 S Proteasome

Andersen

Madsen

Prag

et al. 2009

Journal of Biological Chemistry

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The 26 S proteasome is a large proteolytic machine, which degrades most intracellular proteins. We found that thioredoxin, Txnl1/TRP32, binds to Rpn11, a subunit of the regulatory complex of the human 26 S proteasome. Txnl1 is abundant, metabolically stable, and widely expressed and is present in the cytoplasm and nucleus. Txnl1 has thioredoxin activity with a redox potential of about ؊250 mV. Mutant Txnl1 with one active site cysteine replaced by serine formed disulfide bonds to eEF1A1, a substrate-recruiting factor of the 26 S proteasome. eEF1A1 is therefore a likely physiological substrate. In response to knockdown of Txnl1, ubiquitin-protein conjugates were moderately stabilized. Hence, Txnl1 is the first example of a direct connection between protein reduction and proteolysis, two major intracellular protein quality control mechanisms.

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“…We hypothesized that TUG may specifically disassemble p97 hexamers at a particular site. We used immunofluorescence microscopy to determine if TUG had a unique staining pattern, as is observed for other UBX domaincontaining proteins (14,16,39). Initial studies of HeLa cells showed that TUG was present in both a perinuclear location and in peripheral punctae.…”

Section: P97 Hexamer Disassembly In Vitro Is Not Affected By Nucleomentioning

confidence: 99%

The Ubiquitin Regulatory X (UBX) Domain-containing Protein TUG Regulates the p97 ATPase and Resides at the Endoplasmic Reticulum-Golgi Intermediate Compartment

Orme¹,

Bogan

2012

Journal of Biological Chemistry

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Background: TUG controls a specialized membrane trafficking pathway in adipocytes but is widely expressed. Results: TUG converts p97 ATPase hexamers into monomers and controls Golgi membrane dynamics. Conclusion: Localized disassembly of p97 hexamers may control a generalized trafficking pathway in eukaryotic cells. Significance: Understanding how TUG and p97 function provides insight into regulation of both generalized and specialized membrane trafficking.

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Ubxd1 is a novel co-factor of the human p97 ATPase

Cited by 42 publications

References 55 publications

An Armadillo motif in Ufd3 interacts with Cdc48 and is involved in ubiquitin homeostasis and protein degradation

An Armadillo motif in Ufd3 interacts with Cdc48 and is involved in ubiquitin homeostasis and protein degradation

Thioredoxin Txnl1/TRP32 Is a Redox-active Cofactor of the 26 S Proteasome

The Ubiquitin Regulatory X (UBX) Domain-containing Protein TUG Regulates the p97 ATPase and Resides at the Endoplasmic Reticulum-Golgi Intermediate Compartment

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