CDC48 Antibody
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Description
Definition and Functional Context of CDC48 Antibody
CDC48 antibodies are immunoreagents designed to detect and characterize the Cdc48 protein (also known as p97 or VCP in mammals). These antibodies enable researchers to study:
Protein Homeostasis and Ubiquitination
CDC48 antibodies have been instrumental in demonstrating Cdc48’s role in ubiquitin homeostasis. For example:
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Ubiquitin recycling: Cdc48 deficiency increases polyubiquitinated proteins and depletes free ubiquitin pools, as shown by immunoprecipitation and Western blotting using anti-ubiquitin and anti-Cdc48 antibodies .
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Aggregate resolution: Antibody-based assays revealed that Cdc48 collaborates with cofactors Ufd1/Npl4 to disassemble ubiquitinated aggregates, facilitating proteasomal degradation .
Cell Cycle Regulation
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Cln3 cyclin stability: In cdc48-3 mutants, anti-HA and anti-FLAG antibodies detected reduced nuclear Cln3 levels and accelerated degradation, linking Cdc48 to G1/S transition .
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Mammalian cyclin D1: shRNA-mediated Cdc48 knockdown in 3T3 cells, analyzed via anti-Ccnd1 antibodies, showed decreased nuclear cyclin D1 and delayed cell cycle entry .
Mechanistic Insights
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ERAD and UPS: Cdc48 antibodies confirmed its interaction with Ufd1/Npl4 to retrotranslocate misfolded ER proteins for proteasomal degradation .
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Metabolic dysregulation: Metabolomics in cdc48-3 yeast strains (using anti-Cdc48 antibodies) revealed glycolytic pathway disruptions .
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Phosphorylation-dependent regulation: Anti-FLAG antibodies identified Cdc48’s phosphorylation by CDKs, which stabilizes G1 cyclins .
Protein Sorting Defects
Challenges and Limitations
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Cross-reactivity: Some antibodies (e.g., anti-Ubx2-7) show nonspecific binding in stress conditions .
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Epitope masking: Cdc48’s ATPase activity induces conformational changes, requiring optimized solubilization for IP .
Future Directions
Product Specs
Buffer
Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Form
Liquid
Lead Time
Made-to-order (14-16 weeks)
Synonyms
CDC48 antibody; YDL126CCell division control protein 48 antibody; EC 3.6.4.6 antibody; Cell division cycle protein 48 antibody; Transitional endoplasmic reticulum ATPase homolog antibody
Target Names
CDC48
Uniprot No.
Target Background
Function
CDC48 is an ATP-dependent chaperone that utilizes the energy derived from ATP hydrolysis to exert mechanical force. This force is used to unfold substrate proteins, disassemble protein complexes, and disaggregate protein aggregates. By recruiting and promoting the degradation of ubiquitinated proteins, CDC48 plays a pivotal role in the ubiquitin fusion degradation (UFD) pathway. It also participates in the endoplasmic reticulum-associated degradation (ERAD) pathway, which mediates the cytoplasmic elimination of misfolded proteins exported from the endoplasmic reticulum (ER). CDC48 is essential for the proteasome-dependent processing/activation of MGA2 and SPT23 transcription factors, leading to the subsequent expression of OLE1. Additionally, CDC48 plays a role in the turnover of OLE1, specifically targeting ubiquitinated OLE1 and other proteins to the ERAD pathway. CDC48 regulates ubiquitin-mediated mitochondria protein degradation. It is involved in spindle disassembly, likely by promoting the degradation of spindle assembly factors ASE1 and CDC5 at the end of mitosis. CDC48 is a component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation. CDC48 potentially provides the mechanical force necessary to dislodge polyubiquitinated nascent peptides from the exit channel. CDC48 is required for ribophagy, a process that relocalizes ribosomal particles into the vacuole for degradation in response to starvation. It is a component of the DSC E3 ubiquitin ligase complexes that tag proteins present in Golgi, endosome and vacuole membranes, and function in protein homeostasis under non-stress conditions, supporting a role in protein quality control. Substrates initially bind through the attached polyubiquitin chain to UDF1/NPL4 and then move through the pore of the ATPase rings, where they are unfolded. CDC48 acts on a broad range of proteins, even those that are well-folded, via ubiquitin-binding and unfolding to initiate substrate processing. CDC48 is involved in the degradation of mislocalized tail-anchored transmembrane proteins extracted from the mitochondrion outer membrane by MSP1 and ubiquitinated by DOA10.
Gene References Into Functions
- Identified the Cdc48-Rad23/Dsk2 axis as a major route to the proteasome. PMID: 28525741
- Elucidated the mechanism of Cdc48 from S. cerevisiae using purified components, including Cdc48 itself, its UN cofactor, and model substrates bearing K48-linked polyubiquitin chains. PMID: 28475898
- Investigated how multispanning endoplasmic reticulum membrane proteins, called ERAD-M substrates, maintain substrate solubility during Endoplasmic Reticulum-associated Degradation (ERAD), where they are retrotranslocated to the cytosol as full-length intermediates. The study found that the Cdc48 complex is generally and critically needed for the solubility of retrotranslocated ERAD-M intermediates. PMID: 28077573
- Data demonstrated that Saccharomyces cerevisiae proteins Rqc1, Ltn1, and Cdc48 prevent the aggregation of aberrant proteins that can only appear after C-terminal alanine-threonine tail (CAT-tail) addition by Rqc2. PMID: 27129255
- Upon DNA damage, the Wss1/Cdc48/Doa1 ternary complex is recruited to sumoylated targets and catalyzes SUMO chain extension through a newly recognized SUMO ligase activity. PMID: 26349035
- Tethering of SCF(Dia2) to the replisome progression complex increases the efficiency of ubiquitylation of the Mcm7 subunit of CMG. Correspondingly, loss of tethering is synthetic lethal in combination with a disassembly-defective allele of CDC48. PMID: 26255844
- Concluded that budding yeast Cdc48 functions downstream of the Ub ligases Ltn1 and Ubr1 to release nascent proteins from the ribosome so that they can be degraded by the proteasome. PMID: 23358411
- This study suggests that the ATPase activity of Cdc48p is necessary for fusion of the outer membranes of mitochondria. PMID: 24893221
- Cdc48 segregase is required to break ubiquitylated CMG helicase into its component parts. PMID: 25342810
- Cdc48-Ubx4 acts on the proteasome and uses chaperone activity to promote its nuclear distribution, thereby optimizing the proteasome level for efficient degradation of mitotic regulators. PMID: 24225956
- Cuz1 helps limit the accumulation of ubiquitin conjugates on both the proteasome and Cdc48, suggesting a possible role in the transfer of ubiquitylated substrates from Cdc48 to the proteasome. PMID: 24121501
- The actions of Cdc48p/p97 and the proteasome are tightly coupled during endoplasmic reticulum-associated degradation. PMID: 23536702
- This study identified over 100 highly interconnected genes that affect stress granules and/or P bodies; additional analyses provided evidence that clearance of these mRNP granules is affected by both autophagy and Cdc48/VCP function, thus identifying a new mechanism for clearing these assemblies from the cell. PMID: 23791177
- Data suggest that the Cdc48(Shp1) complex controls Glc7 activity by regulating its interaction with Glc8 and possibly further regulatory subunits. PMID: 23418575
- SUMO-targeted Cdc48 restricts the recombinase Rad51 by counterbalancing the activity of Rad52. PMID: 23624404
- Ubiquitination of the nascent peptide starts on the 80S and continues on the 60S, on which Cdc48 is recruited to escort the substrate for proteasomal degradation. PMID: 23479637
- This study describes a critical role for Cdc48/p97 in signal-induced disassembly of the SCF ubiquitin ligase complex for coordinated inhibition of substrate ubiquitylation. PMID: 23000173
- The results suggest that Cdc48p controls mitochondrial morphology by regulating turnover of proteins involved in mitochondrial morphology in a Vms1p-independent manner. PMID: 22580068
- Data establish Cdc48/p97-Ufd1-Npl4 as a crucial negative regulator of Aurora B early in mitosis of human somatic cells and suggest that the activity of Aurora B on chromosomes needs to be restrained to ensure faithful chromosome segregation. PMID: 21486945
- Dfm1 forms a complex with the AAA-ATPase Cdc48 in a strain lacking the Cdc48 membrane-recruiting component Ubx2. PMID: 20579315
- Ubiquitylation of Sec23 is controlled by the Rsp5 ubiquitin ligase. Cdc48 controls the proteasome-mediated degradation of Sec23. PMID: 20846524
- Data show that the yeast Ubp3-Bre5 deubiquitination complex interacts with both the chaperone-like Cdc48, a major actor of the ubiquitin and proteasome system, and Ufd3, a ubiquitin-binding cofactor of Cdc48. PMID: 20508643
- Cdc48-Shp1 promotes nuclear accumulation of Glc7 to counteract Ipl1 activity. PMID: 20483956
- Ssz1 restores endoplasmic reticulum-associated protein degradation in cells expressing a defective cdc48-ufd1-npl4 complex by upregulating cdc48. PMID: 20038635
- The high-resolution crystal structure of the p97-PLAA complex was solved, showing that the PUL domain forms a 6-mer Armadillo-containing domain. PMID: 19887378
- Dsk2p, Rad23p, and the trimeric Cdc48 complex function together in the delivery of ubiquitinated proteins to the proteasome. PMID: 15167887
- Degradation of CFTR requires the ubiquitin protein ligases Der3p/Hrd1p and Doa10p, as well as the cytosolic trimeric Cdc48p-Ufd1p-Npl4p complex. PMID: 15215312
- Data suggest that Shp1 and Ubx2 are adaptors for Cdc48-dependent protein degradation through the ubiquitin/proteasome pathway. PMID: 15258615
- Cdc48 associates with Ufd2, an E4 multiubiquitylation enzyme that adds further ubiquitin moieties to preformed ubiquitin conjugates to promote degradation. PMID: 16427015
- The PUL and PFU domains of Doa1 promote the formation of a Doa1-Cdc48-ubiquitin ternary complex, potentially allowing for the recruitment of ubiquitinated proteins to Cdc48. PMID: 16428438
- The Hrd1p ligase complex unites substrate selection in the ER lumen and polyubiquitination in the cytoplasm and links these processes to the release of ER proteins via the Cdc48p complex. PMID: 16619026
- There is mitochondrial involvement in Cdc48p/VCP-dependent apoptosis. PMID: 16822868
- Dfm1p interacts with Cdc48p through its SHP boxes, defining a new motif for interaction with this widely employed AAA-ATPase. PMID: 17083136
- One Ufd1-Npl4 heterodimer is shown to interact with one p97 hexamer to form the p97-Ufd1-Npl4 complex. PMID: 17202270
- Cdc48p functions along with the Npl4p-Ufd1p complex as a polyubiquitin-selective segregase. PMID: 17289586
- Cdc48 and Rpt4 have cooperative roles in dislocation of endoplasmic reticulum-associated degradation (ERAD) substrates. PMID: 18174173
- The observation that Ubx2 and Ubx4 are not found together in one complex with Cdc48 suggests several distinct steps in modulating the activity and localization of Cdc48 in the endoplasmic reticulum. PMID: 19359248
- 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. PMID: 19805280
- Findings expand the functional targets of Cdc48 to include active transcriptional regulatory complexes in the nucleus. PMID: 19915556
Database Links
KEGG: sce:YDL126C
STRING: 4932.YDL126C
Protein Families
AAA ATPase family
Subcellular Location
Microsome. Endoplasmic reticulum. Cytoplasm.
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