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Data suggest ATXN3 (zeige ATXN3 Proteine) binds with low-micromolar affinity to both wild-type p97/VCP and mutants linked to proteostasis deficiency multisystem proteinopathy 1 (MSP1; also called hereditary inclusion body myopathy); stoichiometry of binding is one ATXN3 (zeige ATXN3 Proteine) molecule per p97/VCP hexamer in presence of ATP; MSP1 mutants of p97/VCP bind ATXN3 (zeige ATXN3 Proteine) irrespective of nucleotide state. (VCP = valosin-containing protein/ATPase; ATXN3 (zeige ATXN3 Proteine) = ataxin-3 (zeige ATXN3 Proteine))
a substantial proportion of the beta2AR (zeige ADRB2 Proteine) produced is non-functional and VCP plays a key role in the maturation and trafficking of the beta2AR (zeige ADRB2 Proteine).
When HEK293T cells were co-transfected with IQGAP1 and VCP, an immunoprecipitation assay revealed that binding of IQGAP1 with disease-related mutant (R155H or A232E) VCP was markedly reduced compared to wild-type VCP. This suggests that reduction of IQGAP1 and VCP interaction may be associated with the pathophysiology of inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD).
Rare variants in VCP genes are risk for sporadic inclusion body myositis.
Knockdown of the host ubiquitin-dependent segregase VCP/p97, results in loss of IE2 expression, subsequent suppression of early and late gene expression and, ultimately, failure in virus replication. NMS-873, a small molecule inhibitor of VCP, is a potent HCMV antiviral with potential as a novel host targeting therapeutic for HCMV infection.
VCP removes sterically trapped Ku70/80 rings from DNA in double-strand break repair.
Data suggest that AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NFkappaB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation, and chromatin-associated processes, which are regulated by ubiquitination. [REVIEW]
Upon damage, p97 (zeige EIF4G2 Proteine) translocates to lysosomes and there cooperates with a distinct set of cofactors including UBXD1 (zeige UBXN6 Proteine), PLAA (zeige PLAA Proteine), and the deubiquitinating enzyme YOD1 (zeige YOD1 Proteine), which we term ELDR components for Endo-Lysosomal Damage Response.
Data show that inhibition of VCP/p97, or siRNA-mediated ablation of VCP/p97 impairs ultraviolet radiation (UVR)-induced RNA polymerase II (RNAPII) degradation.
p97 (zeige EIF4G2 Proteine) negatively regulates NRF2 (zeige GABPA Proteine) through the canonical pathway by extracting ubiquitylated NRF2 (zeige GABPA Proteine) from the KEAP1 (zeige KEAP1 Proteine)-CUL3 (zeige CUL3 Proteine) E3 complex.
Findings indicate that p97 plays a conserved role in dismantling the CMG helicase complex during different cellular events, but that distinct regulatory signals ultimately control when and where unloading takes place.
p97 is an essential regulator of DNA damage-dependent CDT1 (zeige CDT1 Proteine) destruction
CDC-48/p97 coordinates CDT-1 (zeige CDT1 Proteine) degradation with GINS chromatin dissociation to ensure faithful DNA replication
data reveal an essential pathway that regulates reformation of the nucleus after mitosis and defines ubiquitin-dependent protein extraction as a common mechanism of Cdc48/p97 activity also during nucleus formation
When we introduced CDC48 antisense morpholino oligonucleotides into zebrafish embryos, the morphant embryos were lethal and showed defects in neuronal outgrowth and neurodegeneration.
CDC48 may promote cell cycling and cell proliferation via C-terminal tyrosine phosphorylation during cold acclimation in fish cells
Together, these results suggested that mouse mammary tumor virus Rem (zeige REM1 Proteine) uses a novel p97 (zeige EIF4G2 Proteine)-dependent, Derlin-independent retrotranslocation mechanism distinct from other pathogens to avoid signal peptide ubiquitylation and proteasomal degradation.
cellular phenotypes caused by P137L mutant expression were not isolated observations, and some other IBMPFD disease-related VCP/p97 mutations could lead to similar outcomes
The functional motions of p97 (zeige EIF4G2 Proteine) using symmetric normal modes have been predicted.
results suggest that (i) NLRP3 inflammasome and local IL-1beta((+))F4/80((+))Ly6C((+)) inflammatory macrophages contribute to pathogenesis of VCP-associated myopathy
VCP (valosin-containing protein), together with its cofactor P47 (zeige MFGE8 Proteine) and the endoplasmic reticulum (ER) morphology regulator ATL1 (Atlastin-1 (zeige ATL1 Proteine)), regulates tubular ER formation
Lysine Methylation of the Valosin-Containing Protein (VCP) Is Dispensable for Development and Survival of Mice
Global expression profiling of VCP(R155H/+) mice identified key dysregulated signaling pathways including genes involved in the physiological system development and function, diseases and disorders, and molecular and cellular functions.
The results reveal an unexpected, crucial role of ATP consumption by VCP in determining cell fate in retinitis pigmentosa, and point to a promising new neuroprotective strategy for this currently incurable disease.
Pro(178) and Pro(183) of SelS (zeige SELS Proteine) play important roles in the translocation of p97(VCP) to the ER membrane and protect cells from ER stress
Knockdown or chemical inhibition of p97 (zeige EIF4G2 Proteine) causes robust accumulation of USP33 (zeige USP33 Proteine) due to inhibition of its degradation
results suggest that VCP plays a mechanistic role in releasing WRNp from the nucleolus
rescue experiments with a lethal mfap1 (zeige MFAP1 Proteine) mutant show that the VCP binding region is not essential for Mfap1 (zeige MFAP1 Proteine) function, but may act to increase its stability or activity
Clu (zeige CLU Proteine) is upstream of and binds to VCP in vivo and promotes VCP-dependent Marf (zeige MFN2 Proteine) degradation in vitro Marf (zeige MFN2 Proteine) accumulates in whole muscle lysates of clu (zeige CLU Proteine)-deficient flies and is destabilized upon Clu (zeige CLU Proteine) overexpression. Thus, Clu (zeige CLU Proteine) is essential for mitochondrial homeostasis and functions in concert with Parkin (zeige PARK2 Proteine) and VCP for Marf (zeige MFN2 Proteine) degradation to promote damaged mitochondrial clearance.
results have revealed SUMOylation as a molecular signaling switch to regulate the distribution and functions of VCP during stress response, and suggest that deficiency in VCP SUMOylation caused by pathogenic mutations will render cells vulnerable to stress insults.
The authors propose that VCP sustains sarcoplasmic proteostasis, in part, by controlling the integrity of a dynamic tubular lysosomal network.
Ter94/VCP appears to be an evolutionarily conserved component that regulates BMP (zeige TGFb Proteine)-Smad1 (zeige SMAD1 Proteine)/5/8 signaling.
Data identifies that ter94, Drosophila VCP, as a strong modulator of motor neuron degeneration induced by knockdown of Caz, Drosophila FUS (zeige FUS Proteine)
Valosin-Containing Protein has an essential role in dendrite pruning through regulating mRNA metabolism
VCP was validated as an atlastin (zeige ATL1 Proteine)-interacting protein.
Ter94 ATPase and K11-linked ubiquitination in Ci contribute to the selectivity by proteasomes for partial degradation.
VCP binds to DIAP1 in a ubiquitin- and BIR domain-dependent manner and facilitates its degradation, therefore, establishing a new link between ubiquitin, dendrite pruning and the apoptosis machinery.
The protein encoded by this gene is a member of a family that includes putative ATP-binding proteins involved in vesicle transport and fusion, 26S proteasome function, and assembly of peroxisomes. This protein, as a structural protein, is associated with clathrin, and heat-shock protein Hsc70, to form a complex. It has been implicated in a number of cellular events that are regulated during mitosis, including homotypic membrane fusion, spindle pole body function, and ubiquitin-dependent protein degradation.
15S Mg(2+)-ATPase p97 subunit
, TER ATPase
, transitional endoplasmic reticulum ATPase
, valosin-containing protein
, yeast Cdc48p homolog
, p97 ATPase
, AAA ATPase p97
, Inv protein
, homolog of yeast cdc48
, valosin containing protein
, CG2331 gene product from transcript CG2331-RA
, TRANSITIONAL ENDOPLASMIC RETICULUM ATPASE TER94
, Valosin-Containing protein
, Valosin-containing protein homolog
, complementation group I
, transitional endoplasmic reticulum 94
, transitional endoplasmic reticulum ATPase-like
, Fanconi anemia group G protein
, Fanconi anemia, complementation group G