The 20S Proteasome as an Assembly Platform for the 19S Regulatory Complex

Hendil, Klavs B.; Kriegenburg, Franziska; Tanaka, Keiji; Murata, Shigeo; Lauridsen, Anne-Marie B.; Johnsen, Anders H.; Hartmann‐Petersen, Rasmus

doi:10.1016/j.jmb.2009.09.038

Cited by 51 publications

(54 citation statements)

References 48 publications

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“…These studies show that Rpt-containing subassemblies of PA700 associate with the 20 S proteasome prior to formation of the intact PA700 and indicate that the 20 S proteasome provides a template function for PA700 formation (Fig. 9, lower panel, lower pathway) (26,34). Moreover, subassemblies of PA700 accumulate in yeast genetically defective for normal 20 S proteasome assembly (35).…”

Section: Discussionmentioning

confidence: 96%

“…This finding is consistent with a model in which cellular 26 S proteasome assembly occurs by binding of intact PA700 to the 20 S proteasome. Such a model, however, differs from one presented by others, in which 26 S proteasome is formed by the sequential binding of PA700 subassemblies to the 20 S proteasome (26,34). The mechanisms of these alternative models should result in different fates of Rpt subunits in the absence of 20 S proteasome.…”

Section: S Proteasome Is Not Required For Assembly Of Pa700-mentioning

confidence: 87%

“…Conflicting data, however, have been obtained regarding the role of the 20 S proteasome in both this and subsequent steps of PA700 formation. These conflicts include a possible requirement for 20 S proteasome as a template for base assembly, the mechanism of lid assembly, and the physical and temporal relationship between assembly of the base and the lid (26,34,35). Thus, it remains uncertain whether PA700 is formed as a separate intact entity prior to its binding to 20 S proteasome or whether it is assembled sequentially from subassemblies using 20 S proteasome and perhaps other PA700 subassemblies as templates.…”

mentioning

confidence: 99%

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C Termini of Proteasomal ATPases Play Nonequivalent Roles in Cellular Assembly of Mammalian 26 S Proteasome

Kim

DeMartino

2011

Journal of Biological Chemistry

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The 26 S proteasome comprises two multisubunit subcomplexes as follows: 20 S proteasome and PA700/19 S regulatory particle. The cellular mechanisms by which these subcomplexes assemble into 26 S proteasome and the molecular determinants that govern the assembly process are poorly defined. Here, we demonstrate the nonequivalent roles of the C termini of six AAA subunits (Rpt1-Rpt6) of PA700 in 26 S proteasome assembly in mammalian cells. The C-terminal HbYX motif (where Hb is a hydrophobic residue, Y is tyrosine, and X is any amino acid) of each of two subunits, Rpt3 and Rpt5, but not that of a third subunit Rpt2, was essential for assembly of 26 S proteasome. The C termini of none of the three non-HbYX motif Rpt subunits were essential for cellular 26 S proteasome assembly, although deletion of the last three residues of Rpt6 destabilized the 20 S-PA700 interaction. Rpt subunits defective for assembly into 26 S proteasome due to C-terminal truncations were incorporated into intact PA700. Moreover, intact PA700 accumulated as an isolated subcomplex when cellular 20 S proteasome content was reduced by RNAi. These results indicate that 20 S proteasome is not an obligatory template for assembly of PA700. Collectively, these results identify specific structural elements of two Rpt subunits required for 26 S proteasome assembly, demonstrate that PA700 can be assembled independently of the 20 S proteasome, and suggest that intact PA700 is a direct intermediate in the cellular pathway of 26 S proteasome assembly.

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Section: Discussionmentioning

confidence: 96%

Section: S Proteasome Is Not Required For Assembly Of Pa700-mentioning

confidence: 87%

mentioning

confidence: 99%

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C Termini of Proteasomal ATPases Play Nonequivalent Roles in Cellular Assembly of Mammalian 26 S Proteasome

Kim

DeMartino

2011

Journal of Biological Chemistry

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“…Furthermore, the significance of 26 S proteasome formation from 20 S proteasome and intact PA700 subcomplexes is uncertain because data supporting alternative models of cellular PA700 assembly into the 26 S proteasome have been presented (42). One model features formation of PA700 by sequential addition of multiple PA700 subcomplexes to 20 S proteasome, which serves as a required assembly template (40,53). By this mechanism, intact PA700 would not exist as an isolated cellular complex.…”

Section: Discussionmentioning

confidence: 99%

ATP Binding by Proteasomal ATPases Regulates Cellular Assembly and Substrate-induced Functions of the 26 S Proteasome

Kim

Thompson

et al. 2013

Journal of Biological Chemistry

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Background: ATPase subunits mediate 26 S proteasome assembly and function. Results: Defective ATP binding by some ATPase subunits inhibits proteasome assembly, and proteasomes harboring an ATP binding-defective subunit are impaired for proteolysis, substrate-stimulated gating, and ATPase activity. Conclusion:The proteasome requires normal ATP binding for assembly and function. Significance: Protein substrates promote their own degradation by inducing ATP-dependent proteasome functions.

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“…The assembly mechanism of the 19S regulatory particle and 26S holoenzyme are still not fully elucidated and different assembly pathways, involving chaperones and accessory proteins, have been suggested. [54][55][56][57] Little attention has been given to the exact intracellular location of these assembly steps, especially in vertebrates. Since most of the 19S RP subunits are missing from the 20S + particle, a putative mechanism for nuclear holoenzyme assembly would presumably involve the independent import of the remaining components.…”

Section: The Fast Lane Into the Nucleusmentioning

confidence: 99%