Systematic proteomics of the VCP-UBXD adaptor network identifies a role for UBXN10 in regulating ciliogenesis.
[No authors listed]
摘要
The AAA-ATPase VCP (also known as p97 or CDC48) uses ATP hydrolysis to 'segregate' ubiquitylated proteins from their binding partners. VCP acts through UBX-domain-containing adaptors that provide target specificity, but the targets and functions of UBXD proteins remain poorly understood. Through systematic proteomic analysis of UBXD proteins in human cells, we reveal a network of over 195 interacting proteins, implicating VCP in diverse cellular pathways. We have explored one such complex between an unstudied adaptor UBXN10 and the intraflagellar transport B (IFT-B) complex, which regulates anterograde transport into cilia. UBXN10 localizes to cilia in a VCP-dependent manner and both VCP and UBXN10 are required for ciliogenesis. Pharmacological inhibition of VCP destabilized the IFT-B complex and increased trafficking rates. Depletion of UBXN10 in zebrafish embryos causes defects in left-right asymmetry, which depends on functional cilia. This study provides a resource for exploring the landscape of UBXD proteins in biology and identifies an unexpected requirement for VCP-UBXN10 in ciliogenesis.
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基因功能
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基因
myl7, ubxn7, ubxn10, TIMM23, ABCF2, CDK4, TOPORS, TIMM17B, STUB1, UBE4B, TUBB3, UNC13B, POLD3, SEC24A, PNPLA6, TMED2, ILVBL, SLC27A4, IFT27, FAF1, LACTB, BTBD9, KLHDC3, UBXN10, ADK, UBXN2B, CSNK1E, CSNK1G3, SLC25A10, CSTF1, TTC30B, PPP4R2, FAM91A1, UBXN2A, DSC1, DSG1, ELAVL2, ERCC3, ALDH1B1, ABCB7, ALDH9A1, ALDH3A2, KLHDC10, UNC13A, CLUAP1, EMC1, MYCBP2, EPB41L3, UBXN4, FAF2, VPS13A, ABCF1, UBR2, GCAT, TRAM1, KLHDC2, HSPBP1, MTCH2, YTHDF3, KCTD13, BRWD3, UBXN7, TRAF3IP1, GCDH, RANBP6, ATP2C1, HTRA2, ACAD9, IFT81, SLC25A4, GSK3B, MSH6, MYLPF, PYCR2, HLA-B, HLA-C, HMGB1, MMAB, HSPA2, UBAC2, IDE, ACADM, ACTBL2, ACADSB, ARAF, STT3A, JUN, JUP, KIFC1, KPNA3, MSH2, MYO6, NDUFS2, ATP2B2, ATP2B3, NUP98, ATP4A, P4HB, DERL2, UBXN1, IFT52, RLIM, TIMMDC1, RNF138, ATP6V1H, GET4, HSPB11, PLS3, BRWD1, GAR1, MIOS, POR, POU3F2, VPS13C, CDKAL1, YTHDF1, C1orf27, PPP1CA, PPP1CB, PPP1CC, PHIP, AUP1, IFT57, PPP1R7, FGGY, PPP4C, CDKN2AIP, TTC27, NPLOC4, PPP4R3A, WDR11, TMEM165, HDAC8, UNC45A, NSFL1C, WDR45B, PRPS2, PRPSAP2, PSMA1, TM9SF3, IFT46, PPP4R3B, RHBDD2, PTGS2, ESYT2, RPTOR, IFT80, PEX19, KLHL12, BCKDHB, RDX, RRM2, SDHA, SDHB, TBC1D15, IFT22, SLC7A1, SURF4, TBCD, PPP1R11, TNFAIP1, TRAF2, TUBA4A, TUBG1, UFD1L, VCP, VDAC2, VDAC3, VRK2, ASPSCR1, BAG6, HECTD3, WDR59, TBC1D17, KLHL36, NUP85, UBXN8, TTC26, VCPIP1, IFT74, NUBPL, UBXN6, SETD7, IFT88, SLC38A1, YIPF5, USP11, UBL4A, KCTD10, ACAD11, WDR24, PHF6, CUL2, RAE1, FAM104A, MYH13, SUCLG2, SUCLA2, SQSTM1, TMEM55B, TTC30A, VAPB, VAPA, TRIP10, UBE4A, MAGED1, NPEPPS, CDC42BPB, MORF4L2, UBE3C, IP6K1, SETDB1
原始数据
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文献解读
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