POMP

Last update 08 May 2025

Basic Info

Synonyms

C13orf12, HSPC014, hUMP1

+ [6]

Introduction

Molecular chaperone essential for the assembly of standard proteasomes and immunoproteasomes. Degraded after completion of proteasome maturation. Mediates the association of 20S preproteasome with the endoplasmic reticulum.

100 Clinical Results associated with POMP

100 Translational Medicine associated with POMP

0 Patents (Medical) associated with POMP

134

Literatures (Medical) associated with POMP

10 Jan 2025·Science Advances

Molecular basis for the stepwise and faithful maturation of the 20 S proteasome

Article

Author: Zhang, Yixiao ; Tang, Qianqian ; Liu, Kai ; Han, Yaoyao ; Han, Qian

The proteasome degrades most superfluous and damaged proteins, and its decline is associated with many diseases. As the proteolytic unit, the 20 S proteasome is assembled from 28 subunits assisted by chaperones PAC1/2/3/4 and POMP; then, it undergoes the maturation process, in which the proteolytic sites are activated and the assembly chaperones are cleared. However, mechanisms governing the maturation remain elusive. Here, we captured endogenous maturation intermediates of human 20 S proteasome, which are low abundance and highly dynamic, and determined their structures by cryo–electron microscopy. Through structure-based functional studies, we identified the key switches that remodel and activate the proteolytic sites. Our results also revealed that the POMP degradation is tightly controlled by a dual-checking mechanism, while the α5 subunit senses POMP degradation to induce PAC1/2 release, achieving the full maturation. These findings elucidate mechanisms directing and safeguarding the proteasome maturation and set basis for building proteasomes to counteract the decline of protein degradation in aging and disease.

01 Nov 2024·iScience

Limiting 20S proteasome assembly leads to unbalanced nucleo-cytoplasmic distribution of 26S/30S proteasomes and chronic proteotoxicity

Article

Author: Daga, Rafael R. ; Daga, Rafael R ; Berdún, María Dolores ; Ruiz-Romero, Gabriel ; Hochstrasser, Mark ; Salas-Pino, Silvia

In addition to the degradation of cell-cycle proteins, short-lived, damaged, or unfolded proteins are constantly cleared from cells by the proteasome. During proliferation, the proteasome localizes to the nucleus and cytoplasm; however, the functional relevance of this compartmentalization remains unclear. Here, we show that folding stress increases 26S/30S proteasome activity, which correlates with the upregulation of Ump1, a chaperone involved in 20S assembly. Conversely, ump1 inactivation results in a drop of 20S and 26S/30S proteasomes. Limited 26S/30S proteasomes in ump1-deficient cells accumulate in the nucleus where they degrade mitotic substrates, allowing cells to proceed through mitosis; however, these cells present cytoplasmic aggregates and constitutive activation of the heat shock response. Thus, our data suggest that an increase in proteasome assembly induced by folding stress functions as an additional layer to proteasome regulation and highlight the importance of balanced proteasome compartmentalization to sustain cell proliferation while maintaining proper cytoplasmic proteostasis.

01 Nov 2024·Life Science Alliance

Structural roles of Ump1 and β-subunit propeptides in proteasome biogenesis

Article

Author: Mark, Eric ; Wendler, Petra ; Dohmen, R Jürgen ; Ramos, Paula C ; Kayser, Fleur ; Höckendorff, Jörg

The yeastpre1-1(β4-S142F) mutant accumulates late 20S proteasome core particle precursor complexes (late-PCs). We report a 2.1 Å cryo-EM structure of this intermediate with full-length Ump1 trapped inside, and Pba1-Pba2 attached to the α-ring surfaces. The structure discloses intimate interactions of Ump1 with β2- and β5-propeptides, which together fill most of the antechambers between the α- and β-rings. The β5-propeptide is unprocessed and separates Ump1 from β6 and β7. The β2-propeptide is disconnected from the subunit by autocatalytic processing and localizes between Ump1 and β3. A comparison of different proteasome maturation states reveals that maturation goes along with global conformational changes in the rings, initiated by structuring of the proteolytic sites and their autocatalytic activation. In thepre1-1strain, β2 is activated first enabling processing of β1-, β6-, and β7-propeptides. Subsequent maturation of β5 and β1 precedes degradation of Ump1, tightening of the complex, and finally release of Pba1-Pba2.

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POMP

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