Proteomics

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Stabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells to augment glioblastoma malignancy

ABSTRACT: he unique prolyl isomerase Pin1 that promotes protein conformational changes is a pivotal therapeutic target in many cancers, but little is known about the regulation of Pin1 protein stability. We previously found that Pin1 was highly expressed in glioma stem cells (GSCs) relative to non-stem tumor cells (NSTCs). Interestingly, treatment of the proteasome inhibitor MG132 markedly restored Pin1 protein expression in NSTCs to a level similar to GSCs. We therefore sought to identify the molecular regulators controlling the proteasomal degradation of Pin1 by mass spectrometry analysis of Pin1-interacting proteins in GSCs. The results showed that Pin1 interacts with a deubiquitinase USP34 in GSCs, suggesting that Pin1 may be stabilized by USP34.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Suspension Culture, Stem Cell

DISEASE(S): Brain Glioblastoma Multiforme

SUBMITTER: Wenchao Zhou  

LAB HEAD: Wenchao Zhou

PROVIDER: PXD041043 | Pride | 2024-01-26

REPOSITORIES: Pride

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T4121_IgG_20200808.dat Other
T4121_IgG_20200808.fasta Fasta
T4121_IgG_20200808.mgf Mgf
T4121_IgG_20200808.raw Raw
T4121_Pin1_20200808.dat Other
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Publications

Stabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells.

Zhu Qiuhong Q   Liang Panpan P   Meng Hao H   Li Fangzhen F   Miao Wei W   Chu Cuiying C   Wang Wei W   Li Dongxue D   Chen Cong C   Shi Yu Y   Yu Xingjiang X   Ping Yifang Y   Niu Chaoshi C   Wu Hai-Bo HB   Zhang Aili A   Bian Xiu-Wu XW   Zhou Wenchao W  

Nature communications 20240102 1

The peptidyl-prolyl cis-trans isomerase Pin1 is a pivotal therapeutic target in cancers, but the regulation of Pin1 protein stability is largely unknown. High Pin1 expression is associated with SUMO1-modified protein hypersumoylation in glioma stem cells (GSCs), but the underlying mechanisms remain elusive. Here we demonstrate that Pin1 is deubiquitinated and stabilized by USP34, which promotes isomerization of the sole SUMO E2 enzyme Ubc9, leading to SUMO1-modified hypersumoylation to support G  ...[more]

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