PSMD10 and PAAF1 bind PSMC4:PSMC5

Stable Identifier
R-HSA-9907979
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
3/5
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PSMD10 and PAAF1 bind PSMC4:PSMC5
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During the assembly of the proteasome 19S regulatory particle (19S RP) base of the 26S proteasome, the PSMC4:PSMC5 dimer (orthologous to yeast Rpt3:Rpt6 dimer) is bound by two chaperone proteins PSMD10 (orthologous to yeast Nas6, also known as gankyrin or p28) and PAAF1 (orthologous to yeast Rpn14) (reviewed in Tomko and Hochstrasser 2013). Formation of the PSMD10:PSMC4:PSMC5:PAAF1 tetramer was confirmed in human embryonic kidney cell line HEK293T (Kaneko et al. 2009). Direct interaction between human PAAF1 and PSMC5 was reported in human cervical carcinoma cell line HeLa (Park et al. 2005). Knockdown of PAAF1 in HEK293T cells does not cause an obvious phenotype in HEK293T cells (Kaneko et al. 2009) and was reported to enhance proteasome activity in HeLa cells (Park et al. 2005). Interactions of human PSMD10, PSMC4, PSMC5, and PAAF1 with each other and the surrounding proteins in different 19S RP conformations were structurally characterized by cryogenic electron microscopy (cryo-EM) (Lu et al. 2017).

Using mouse as a model system, it was found that excess PSMC5 was targeted by HERC1 ubiquitin ligase, which is recruited to unassembled PSMC5 by its chaperone PAAF1 (Zavodszky et al. 2021). HERC1 may also target the unassembled PSMC4:PSMC5 heterodimers (Zavosdszky et al. 2021). A missense mutant of HERC1 impaired in the recognition and ubiquitination of the PSMC5:PAAF1 complex causes neurodegeneration in mice (Zavodszky et al. 2021).
Literature References
PubMed ID Title Journal Year
28689658 Conformational Landscape of the p28-Bound Human Proteasome Regulatory Particle

Lu, Y, Wu, J, Dong, Y, Chen, S, Sun, S, Ma, YB, Ouyang, Q, Finley, D, Kirschner, MW, Mao, Y

Mol Cell 2017
15831487 Proteasomal ATPase-associated factor 1 negatively regulates proteasome activity by interacting with proteasomal ATPases

Park, Y, Hwang, YP, Lee, JS, Seo, SH, Yoon, SK, Yoon, JB

Mol Cell Biol 2005
19490896 Assembly pathway of the Mammalian proteasome base subcomplex is mediated by multiple specific chaperones

Kaneko, T, Hamazaki, J, Iemura, S, Sasaki, K, Furuyama, K, Natsume, T, Tanaka, K, Murata, S

Cell 2009
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Authored
Orlic-Milacic, M  (2024-04-22)
Created
Orlic-Milacic, M  (2024-04-18)
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