TY  - JOUR
A1  - Körner, Maria
A1  - Meyer, Susanne R.
A1  - Marincola, Gabriella
A1  - Kern, Maximilian J.
A1  - Grimm, Clemens
A1  - Schuelein-Voelk, Christina
A1  - Fischer, Utz
A1  - Hofmann, Kay
A1  - Buchberger, Alexander
T1  - The FAM104 proteins VCF1/2 promote the nuclear localization of p97/VCP
JF  - eLife
N2  - The ATPase p97 (also known as VCP, Cdc48) has crucial functions in a variety of important cellular processes such as protein quality control, organellar homeostasis, and DNA damage repair, and its de-regulation is linked to neuromuscular diseases and cancer. p97 is tightly controlled by numerous regulatory cofactors, but the full range and function of the p97–cofactor network is unknown. Here, we identify the hitherto uncharacterized FAM104 proteins as a conserved family of p97 interactors. The two human family members VCP nuclear cofactor family member 1 and 2 (VCF1/2) bind p97 directly via a novel, alpha-helical motif and associate with p97-UFD1-NPL4 and p97-UBXN2B complexes in cells. VCF1/2 localize to the nucleus and promote the nuclear import of p97. Loss of VCF1/2 results in reduced nuclear p97 levels, slow growth, and hypersensitivity to chemical inhibition of p97 in the absence and presence of DNA damage, suggesting that FAM104 proteins are critical regulators of nuclear p97 functions.
KW  - p97 VCP Cdc48
KW  - ubiquitin proteasome system
KW  - nuclear import
KW  - DNA damage repair
KW  - FAM104A
KW  - FLJ14775
KW  - FAM104B
KW  - FLJ20434
KW  - CXorf44
KW  - cell biology
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350222
VL  - 12
ER  -