High impact information on UFD1

• Therefore, Cdc48/p97-Ufd1-Npl4 is an essential chaperone that regulates transformation of the microtubule structure as cells reenter interphase [1].
• In the absence of p97-Ufd1-Npl4 function, microtubules in Xenopus egg extracts remain as monopolar spindles attached to condensed chromosomes after Cdc2 kinase activity has returned to the interphase level [1].
• PIP2 and PIP3: complex roles at the cell surface [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].

Biological context of UFD1

• Here, we present the solution structure of yeast Ufd1 N domain and show that it has two distinct binding sites for mono- and polyubiquitin [5].
• Here, we discuss the possibility that the Cdc48/ p97-Ufd1-Npl4 complex has a more general role in mediating morphological transitions as the cell exits mitosis and enters G(1) [6].
• With the noninvestigated exception of haptophytes a phylogenetically and mechanistically related system is apparently present in all chromalveolates with 4 membrane-bound plastids because amongst others, PPC-specific Derlins (Der1-like proteins), CDC48 and its cofactor Ufd1 were identified in the nuclear genomes of diatoms and apicomplexa [7].
• The Uba2 and Ufd1 proteins of Saccharomyces cerevisiae interact with poly(A) polymerase and affect the polyadenylation activity of cell extracts [8].
• A S. pombe mutant containing a frameshift mutation at the beginning of the carboxy-terminal half of gene ufd1 (the Saccharomyces cerevisiae UFD1 homologue) is cordycepin-resistant and sterile [9].

Anatomical context of UFD1

• 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 [10].
• 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].
• The AAA ATPase Cdc48/p97 together with its adaptors, Ufd1-Npl4, regulate membrane-related functions and mitotic spindle disassembly by directly binding to membrane-associated proteins or spindle assembly factors, modulating their interactions with membranes or spindles, respectively [6].
• Valosin-containing Protein (p97) Is a Regulator of Endoplasmic Reticulum Stress and of the Degradation of N-End Rule and Ubiquitin-Fusion Degradation Pathway Substrates in Mammalian Cells [11].

Associations of UFD1 with chemical compounds

• Polyubiquitin chains linked by lysine 48 are recognized in a synergistic manner by both p97 and an evolutionarily conserved ubiquitin-binding site at the NH2 terminus of Ufd1 [4].

Physical interactions of UFD1

• Neither cytosolic chaperones nor Cdc48p/Ufd1p/Npl4p complex components or proteasome activity are required for ER exit, indicating that K28 retrotranslocation is mechanistically different from classical ER-associated protein degradation (ERAD) [12].
• Both Uba2 and Ufd1 can be co-immunoprecipitated from extracts with Pap1, confirming in vitro the interaction identified by two-hybrid analysis [8].

Other interactions of UFD1

• We also found that each member of the Cdc48p-Ufd1p-Npl4p complex is individually required for ERAD [13].
• We show that these two proteins are probably delivery factors for ubiquitinated ER substrates to the proteasome, following their removal from the membrane via the Cdc48-Ufd1-Npl4p complex [14].
• Two of the five genes thus identified, UFD1 and UFD5, function at post-ubiquitination steps in the UFD pathway [15].
• The Ufd1-ubiquitin interaction is essential for transfer of substrates to the proteasome [5].
• To determine the property of Ufd2, we reconstituted the UFD pathway using purified enzymes from yeast [16].

References