High impact information on NPL4

• Therefore, Cdc48/p97-Ufd1-Npl4 is an essential chaperone that regulates transformation of the microtubule structure as cells reenter interphase [1].
• Remarkably, this enzyme binds preferentially ubiquitinated substrates, suggesting that CDC48(UFD1/NPL4) is qualified to selectively remove ubiquitin conjugates from protein complexes [2].
• Formation of a closed NE requires the p97-Ufd1-Npl4 complex, not previously implicated in membrane fusion [3].
• Here, we have studied the mechanism by which the p97-Ufd1-Npl4 complex functions in this retrotranslocation pathway [4].
• We found that CDC48(UFD1/NPL4) plays a second role in the OLE pathway by mediating ERAD of OLE1 [5].

Biological context of NPL4

• The HRD4 gene was identical to NPL4, a gene previously implicated in nuclear transport [6].
• Fluorescence in situ hybridization experiments on human metaphases localized the NPL4 gene on the most telomeric region of chromosome 17q [7].
• Our data indicate that this lack of proteasomal processing of ubiquitinated proteins constitutes the primary defect in hrd4/npl4 mutant cells and explains the diverse set of hrd4/npl4 phenotypes [6].
• Here, we report that the AAA-ATPase Cdc48/p97 and its adapters Ufd1-Npl4, which have a well-established role in membrane functions, also regulate spindle disassembly by modulating microtubule dynamics and bundling at the end of mitosis [1].
• The Cdc48/p97-Ufd1-Npl4 complex: its potential role in coordinating cellular morphogenesis during the M-G1 transition [8].

Anatomical context of NPL4

• The only functional data available about mammalian Ufd1p is the ability to form a complex with the rat Npl4 protein, a component of the nuclear pore complex [7].
• Nuclear transport defects and nuclear envelope alterations are associated with mutation of the Saccharomyces cerevisiae NPL4 gene [9].
• Function of the p97-Ufd1-Npl4 complex in retrotranslocation from the ER to the cytosol: dual recognition of nonubiquitinated polypeptide segments and polyubiquitin chains [4].

Other interactions of NPL4

• We also found that each member of the Cdc48p-Ufd1p-Npl4p complex is individually required for ERAD [6].
• In addition, we demonstrate that polyubiquitinated Mga2p120 accumulates in cells lacking Npl4p or proteasome function and Rsp5p is required for Mga2p120 polyubiquitination [10].
• By determining the differential abundance of ubiquitinated proteins in yeast mutated for NPL4 and UBC7, which are major components of ER-associated degradation (ERAD), we furthermore were able to classify 83 of these identified ubiquitinated membrane proteins as potential endogenous substrates of the ERAD pathway [11].
• In combination, our characterization of GET3 genetic and biochemical interactions with NPL4, GET1, and GET2 implicates Get3 in multiple membrane-dependent pathways [12].
• Cdc48-Ufd1-Npl4: stuck in the middle with Ub [13].

References