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  - 
TY  - JOUR
A1  - Pascoalino, Bruno
A1  - Dindar, Gülcin
A1  - Vieira-da-Rocha, João P.
A1  - Machado, Carlos Renato
A1  - Janzen, Christian J.
A1  - Schenkman, Sergio
T1  - Characterization of two different Asf1 histone chaperones with distinct cellular localizations and functions in Trypanosoma brucei
JF  - Nucleic Acids Research
N2  - The anti-silencing function protein 1 (Asf1) is a chaperone that forms a complex with histones H3 and H4 facilitating dimer deposition and removal from chromatin. Most eukaryotes possess two different Asf1 chaperones but their specific functions are still unknown. Trypanosomes, a group of early-diverged eukaryotes, also have two, but more divergent Asf1 paralogs than Asf1 of higher eukaryotes. To unravel possible different functions, we characterized the two Asf1 proteins in Trypanosoma brucei. Asf1A is mainly localized in the cytosol but translocates to the nucleus in S phase. In contrast, Asf1B is predominantly localized in the nucleus, as described for other organisms. Cytosolic Asf1 knockdown results in accumulation of cells in early S phase of the cell cycle, whereas nuclear Asf1 knockdown arrests cells in S/G2 phase. Overexpression of cytosolic Asf1 increases the levels of histone H3 and H4 acetylation. In contrast to cytosolic Asf1, overexpression of nuclear Asf1 causes less pronounced growth defects in parasites exposed to genotoxic agents, prompting a function in chromatin remodeling in response to DNA damage. Only the cytosolic Asf1 interacts with recombinant H3/H4 dimers in vitro. These findings denote the early appearance in evolution of distinguishable functions for the two Asf1 chaperons in trypanosomes.
KW  - chromatin assembly factors
KW  - DNA-damage checkpoint
KW  - tousled-like kinases
KW  - saccharomyes cerevisiae
KW  - gene expression
KW  - acetyltransferase RTT109
KW  - african trypanosomes
KW  - antigenetic variation
KW  - cycle regulation
KW  - nuclear import
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117220
SN  - 1362-4962
VL  - 42
IS  - 5
ER  -