Last update 01 Nov 2024

PPP2R2B

Last update 01 Nov 2024

Basic Info

Synonyms

B55beta, PP2A subunit B isoform B55-beta, PP2A subunit B isoform beta

+ [8]

Introduction

The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. Within the PP2A holoenzyme complex, isoform 2 is required to promote proapoptotic activity (By similarity). Isoform 2 regulates neuronal survival through the mitochondrial fission and fusion balance (By similarity).

Drugs associated with PPP2R2B

SRT-424

Target

PPP2R2B

Mechanism

PPP2R2B gene modulators

Active Org.-

Originator Org.

Smart Therapeutics, Inc.

Active Indication-

Inactive Indication

Spinocerebellar Ataxias

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PPP2R2B

100 Translational Medicine associated with PPP2R2B

0 Patents (Medical) associated with PPP2R2B

180

Literatures (Medical) associated with PPP2R2B

01 Dec 2024·Cellular and Molecular Life Sciences

Nuclear translocation of ISG15 regulated by PPP2R2B inhibits cisplatin resistance of bladder cancer

Article

Author: Wang, Yinghan ; Zhu, Jiangquan ; Zhang, Lizhen ; Chen, Wei ; Dong, Zhong ; Lu, Jun ; Feng, Zihao ; Huang, Gaowei ; Dai, Ziran ; Liu, Jinwen ; Luo, Chenggong ; Chen, Zhenhua ; Luo, Junhang ; Yu, Anze

AbstractCisplatin resistance is a major challenge for systemic therapy against advanced bladder cancer (BC). Little information is available on the regulation of cisplatin resistance and the underlying mechanisms require elucidation. Here, we detected that downregulation of the tumor suppressor, PPP2R2B (a serine/threonine protein phosphatase 2 A regulatory subunit), in BC promoted cell proliferation and migration. What’s more, low PPP2R2B expression was correlated with cisplatin resistance. In vitro and in vivo experiments verified that PPP2R2B could promote BC sensitivity to cisplatin. In terms of mechanism, we identified a novel function of PPP2R2B as a nucleocytoplasmic transport molecule. PPP2R2B promoted ISG15 entry into the nucleus by mediating binding of IPO5 with ISG15. Nuclear translocation of ISG15 inhibited DNA repair, further increasing ISG15 expression through activation of the STING pathway. Besides, PPP2R2B was down-regulated by SUV39H1-mediated histone 3 lysine 9 trimethylation, which could be restored by the SUV39H1-specific inhibitor, chaetocin. Our data suggest that PPP2R2B expression level is a potential biomarker for chemotherapy response and that chemotherapy in combination with chaetocin may be a feasible treatment strategy for patients with BC.

01 Dec 2024·Molecular Biology Reports

Early-onset familial essential tremor is associated with nucleotide expansions of spinocerebellar ataxia in China

Article

Author: Cao, Lanxiao ; Tian, Jun ; Yan, Yaping ; Zhou, Chen ; Zhao, Guohua ; Pu, Jiali ; Yin, Xinzhen ; Zhao, Gaohua ; Zhu, Zeyu ; Zheng, Zhilin ; Lu, Jinyu ; Chen, Yanxing ; Zhang, Baorong ; Lv, Dayao

BACKGROUNDEssential tremor (ET) is a neurological disease characterized by action tremor in upper arms. Although its high heritability and prevalence worldwide, its etiology and association with other diseases are still unknown.METHODWe investigated 10 common spinocerebellar ataxias (SCAs), including SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, SCA17, SCA36, dentatorubral-pallidoluysian atrophy (DRPLA) in 92 early-onset familial ET pedigrees in China collected from 2016 to 2022.RESULTWe found one SCA12 proband carried 51 CAG repeats within PPP2R2B gene and one SCA3 proband with intermediate CAG repeats (55) with ATXN3 gene. The other 90 ET probands all had normal repeat expansions.CONCLUSIONTremor can be the initial phenotype of certain SCA. For early-onset, familial ET patients, careful physical examinations are needed before genetic SCA screening.

01 Oct 2024·Movement Disorders

Role of Bβ1 overexpression in the pathogenesis of SCA12

Article

Author: Liu, Hans B. ; Zhou, Chengqian ; Deng, Leon ; Margolis, Russell L. ; Li, Pan P. ; Dong, Tao ; Tang, Fan

AbstractBackgroundSpinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by a CAG/CTG repeat expansion at the PPP2R2B locus.ObjectiveWe investigated how the CAG repeat expansion within the PPP2R2B 7B7D transcript influences the expression of Bβ1 and a potential protein containing a long polyserine tract.MethodsTranscript and protein expression were measured using quantitative PCR (qPCR) and Western blot, respectively, in an SK‐N‐MC cell model that overexpresses the full‐length PPP2R2B 7B7D transcript. The apoptotic effect of a protein containing a long polyserine tract on SK‐N‐MC cells was evaluated using caspase 3/7 activity.ResultsThe CAG repeat expansion increases the expression of the PPP2R2B 7B7D transcript, as well as Bβ1 protein, in an SK‐N‐MC cell model in which the full‐length PPP2R2B 7B7D transcript is overexpressed. The CAG repeat expansion within the 7B7D transcript is translated into a long polyserine tract that triggers apoptosis in SK‐N‐MC cells.ConclusionsThe SCA12 mutation leads to overexpression of PPP2R2B Bβ1 and to expression of a protein containing a long polyserine tract; both these effects potentially contribute to SCA12 pathogenesis. © 2024 International Parkinson and Movement Disorder Society.

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