VCP-NPL4-UFD1 AAA ATPase complex

Definition

Target type: cellularcomponent

A multiprotein ATPase complex required for the efficient dislocation of ER-lumenal degradation substrates, and their subsequent proteolysis by the proteasome. In budding yeast, this complex includes Cdc48p, Npl4p and Ufd1p proteins. In mammals, this complex includes a hexamer of VCP/p97 (a cytosolic ATPase) and trimers of each of its cofactors UFD1L and NPL4 (NPLOC4) (e.g. a 6:3:3 stoichiometry). [PMID:11813000, PMID:16179952]

The VCP-NPL4-UFD1 AAA ATPase complex is a cellular machine that plays a critical role in protein quality control and ubiquitin-dependent proteolysis. It is a multi-subunit complex consisting of three core components:

* **Valosin-containing protein (VCP)**: Also known as p97, this is the central ATPase subunit. It possesses two AAA domains that bind and hydrolyze ATP to drive the complex's activity. VCP acts as a molecular "disaggregase" by extracting misfolded or aggregated proteins from complexes.

* **NPL4**: This is a ubiquitin-binding protein that acts as a substrate receptor. It recognizes ubiquitinated proteins and delivers them to the VCP complex. NPL4 plays a key role in targeting misfolded proteins for degradation.

* **UFD1**: This is a ubiquitin-binding protein that acts as a cofactor for NPL4. It aids in the recruitment and stabilization of NPL4 on ubiquitinated proteins.

These three components associate dynamically to form a functional complex that operates within the cytoplasm and nucleus of eukaryotic cells.

The complex is embedded within a dynamic cellular network, interacting with a diverse array of cofactors and substrates. These interactions allow the VCP-NPL4-UFD1 complex to participate in a wide range of cellular processes, including:

* **ER-associated degradation (ERAD)**: This pathway removes misfolded proteins from the endoplasmic reticulum (ER), a key organelle involved in protein folding and secretion. The VCP complex extracts these misfolded proteins from the ER membrane and delivers them to the proteasome for degradation.

* **Autophagy**: This cellular process involves the engulfment and degradation of damaged organelles and protein aggregates. The VCP complex contributes to autophagy by extracting ubiquitinated cargo from autophagosomes, the vesicles that enclose cellular material destined for degradation.

* **DNA repair**: The complex is involved in the repair of damaged DNA by extracting misfolded proteins from DNA repair complexes.

* **Cell cycle control**: VCP is essential for the proper progression of the cell cycle, particularly during mitosis. It plays a role in the disassembly of protein complexes and the release of factors required for cell division.

* **Signaling pathways**: The complex can regulate signaling pathways by controlling the stability and activity of signaling proteins.

In summary, the VCP-NPL4-UFD1 AAA ATPase complex is a vital component of cellular homeostasis, ensuring the proper folding and degradation of proteins. It plays a crucial role in a diverse range of cellular processes, maintaining cellular integrity and function.'
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Proteins (1)

Compounds (6)