Review Article

Cdc48: A Swiss Army Knife of Cell Biology

Table 1

Functions and substrates of some Cdc48 cofactors.

Cofactor Function Substrates

Ufd1-Npl4 ERAD, cell cycle control, nuclear transport, DNA repair, transcription, ribosome-associated degradation, essential for cell growth, clearance of damaged mitochondria Spt23, Mga2, Sec23, Mps1, Ole1, Hmg2, CPY*, CT*, CTG*, Ste6*, Pex29, Rad52, Rpb1, Matα2, Gnd1PTC, GFHNS, Fbp1, UFD model substrates, Ci/Gli3, CD3δ, CD4, TCRα, HO-1, CDT1, SET8, tyrosinase mutant, L3MBTL1, SKP2, MHC class I heavy chains, inositol 1, 4,5-triphosphate receptors, Hmg-CoA reductase…

Ufd2/E4B Ubiquitin chain synthesis, cell cycle control, ERAD, cardiac development, and nervous system maintenance Mps1, Pex29, Ste6*, Hmg2, Spt23, Fad3, UFD model substrates, p53, p73, Ataxin-3, Fez1, myosin chaperone UNC-45

Ufd3/PLAAUbiquitin homeostasis, ribophagy, tRNA import to mitochondria, DNA repair, multivesicular body sorting Cse4, Rpl25, Spt23, Cps1, Vph1, Fad3, UFD model substrates, PCNA, histone H2B, N-end rule

Vms1/ANKZF-1 ERAD, mitochondria stress response Cdc13, Fzo1, CFTR, CPY*

Ubx1/p47/Shp1 Autophagy, nuclear envelop formation, ER biogenesis, Golgi assembly GFP-Osh1, Fad3, UFD model substrates, NEMO, Rum1

Ubx2 ERAD, lipid droplet maintenance Hmg2, CPY*, KSS, Ubc6*, Sec61-2, Deg1-GFP, Spt23, SREBP, RNA binding protein HuR, Insig-1, ApoB-100, UBC6-B5 mutant

Ubx3 Unknown Unknown

Ubx4 ERAD, DNA repair CPY*, Ste6*, Fbp1, Rpb1

Ubx5 Links Cdc48 to CRL E3 ligases Rpb1, HIF1α

Ubx6 Unknown Unknown

Ubx7 Unknown, in complex with Dfm1 Unknown

FAF1 ERAD, proapoptosis factor CD3δ, Hsp70, β-catenin

Ataxin-3 Ubiquitin chain editing, ERAD, stress response TCRα, BACE mutant, SOD1, PARKIN, CHIP, integrin subunits, UFD model substrates

Substrates of Cdc48 cofactors in yeast S. cerevisiae are indicated in bold.