Ask about this productRelated genes to: PPP2R5A Blocking Peptide
- Gene:
- PPP2R5A NIH gene
- Name:
- protein phosphatase 2 regulatory subunit B'alpha
- Previous symbol:
- -
- Synonyms:
- PR61A, B56A, B56alpha
- Chromosome:
- 1q32.3
- Locus Type:
- gene with protein product
- Date approved:
- 1996-05-08
- Date modifiied:
- 2017-04-05
Related products to: PPP2R5A Blocking Peptide
Related articles to: PPP2R5A Blocking Peptide
- p62/SQSTM1 self-assembles with polyubiquitin into liquid-like condensates ("p62 bodies") that function as stress-signaling hubs and selective autophagy cargo. We show that TBK1-dependent phosphorylation at Ser403 acts as a threshold-dependent modulator of a condensate's physical properties and promotes their rapid autophagic clearance. Phosphorylation within p62 bodies drives a transition from large, fluid droplets to compact, gel-like condensates that efficiently capture LC3-positive isolation membranes and accelerate the autophagic removal of ubiquitinated proteins. PP2A holoenzymes containing PPP2R5A/B/E, recruited via a KEAP1 bridge, counteract TBK1 by dephosphorylating Ser403. Homozygous p62S403E/S403E knock-in embryonic stem cells differentiate into post-mitotic neurons enriched in miniaturized, gel-like p62 bodies. Consistently, phosphorylation-mimetic knock-in mice show similar remodeling of p62 condensates in vivo, demonstrating that this phosphorylation-driven mechanism maintains proteostasis across scales. We propose that Ser403 phosphorylation functions as a molecular switch that couples the material state of p62 condensates to their stability and serves as a central control point for p62-mediated protein degradation. - Source: PubMed
Publication date: 2026/05/05
Komatsu-Hirota SatokoTabata KeisukeSou Yu-ShinKakuta SoichiroSakamaki Jun-IchiTsuchiya HikaruLi JiachenKumeta HiroyukiSakai YujiFujioka YukoNoshiro DaisukeShimobayashi Shunsuke FKurimura TomoTaniguchi TakashiAbe ManabuKoike MasatoMorishita HideakiNoda Nobuo NKomatsu Masaaki - The transcription factor c-Myc is a master oncoprotein that regulates over 15% of all genes. Protein phosphatase 2A (PP2A), a crucial tumor suppressor, destabilizes c-Myc protein. Classically, PP2A-mediated dephosphorylation of Ser62 followed by Thr58 phosphorylation was thought to promote ubiquitination of c-Myc by the E3 ligase F-box and WD repeat domain containing 7 (FBXW7). However, recent evidence indicates that FBXW7 preferentially recognizes c-Myc when both Thr58 and Ser62 are phosphorylated, leaving the mechanism underlying PP2A-induced c-Myc degradation unsolved. Here, we demonstrate that the PP2A-B55α complex, which directly dephosphorylates c-Myc at Thr58, regulates two distinct degradation pathways in a biphasic manner: B55α suppression increases Thr58 phosphorylation and enhances FBXW7-dependent degradation, whereas B55α overexpression promotes Thr58-independent, ubiquitin-protein ligase E3 component N-recognin 5 (UBR5)-mediated degradation. We further show that the PP2A-B55α complex binds and dephosphorylates UBR5. In contrast, B55δ, which belongs to the same B55 family and shares a common core structure, exhibits weaker UBR5 binding affinity and fails to induce c-Myc degradation. Our findings identify PP2A-B55α as a context-dependent molecular switch for c-Myc degradation and provide a unified framework that resolves the paradox linking PP2A activation to c-Myc destabilization. - Source: PubMed
Publication date: 2026/03/12
Ando SanaIkeda ShuntaTanaka KeikoTomabechi YuriYamagata AtsushiShirouzu MikakoTsunedomi RyouichiNagano HiroakiTsuji ShunyaSato KoichiOhama Takashi - Colorectal cancer (CRC) is one of the leading causes of death worldwide. Colorectal cancer stem cells (CCSCs) are a critical, rare cell subpopulation that drives their malignant progression, treatment resistance, and tumor recurrence. Understanding the developmental mechanisms of CCSCs is crucial for elucidating tumor evolution and identifying potential therapeutic targets. Proteomics, as a high-throughput protein detection method, has been widely used to detect the mechanisms of tumor occurrence and development. However, the scarcity of CCSCs makes obtaining sufficient serial samples for traditional proteomics studies challenging. Herein, we constructed a multi-omics platform to study CCSCs' dynamic development based on a low-cell-number proteomics, transcriptome and metabolomics (LCNP-T-M). LCNP achieved the identification of 5774 - 5992 proteins under low-input conditions, which significantly enhanced proteome coverage. By the LCNP-T-M platform, we identified seven key regulatory factors: ROCK1, PPP2R5A, RHOA, JUN, GCLM, PIK3CB, and AK6. RT-qPCR revealed their stage-specific overexpression during CCSCs induction and showed their potential as therapeutic targets. The LCNP-T-M platform provides an effective technical framework and theoretical foundation for investigating CCSCs' mechanisms and target discovery. - Source: PubMed
Publication date: 2025/12/12
Chen TianLi BoyeZhou SinongZhang WenmeiWang LiangxiaWang MengyingZhao WeijianWang Xiayan - Protein phosphatase 2A (PP2A), a pivotal serine/threonine phosphatase, plays a crucial role in cellular regulation and tumor suppression. Dysregulation of PP2A complex, particularly the Aα subunit and B56 family, is linked to malignancies through altered substrate interactions, exemplified by c-MYC dynamics. Given the challenges in identifying PP2A substrates-owing to the enzyme's expansive substrate range, transient interaction profiles, and complex regulatory mechanisms-we employed bioluminescence resonance energy transfer (BRET) sensors. These advanced molecular tools facilitate the real-time detection of protein-protein interactions within live cells. This investigation details the creation and application of a novel PPP2R5A (B56α) BRET sensor tailored for cytosolic and nuclear environments, effectively distinguishing specific PP2A interactions. The nuclear sensor, enhanced with a nuclear localization signal, enabled probing of targets like c-MYC. The dual compartmental utility of these sensors underscores their significant potential in elucidating PP2A's regulatory roles and their implications in oncogenesis. Our study highlights the efficacy of BRET sensors in formulating precision therapeutic strategies. This advancement provides a robust framework for deeper investigations into the multifaceted roles of PP2A in both normal physiological and pathological contexts, paving the way for future explorations into its intricate molecular interactions. - Source: PubMed
Publication date: 2025/06/27
Yamauchi HirofumiOishi AtsuroAjiro MasahikoNakayama AtsuhitoNishimura KazukiKurikawa MichikoYoshida MinaKudo ReiKoizumi MinoriIzumi-Tamura TakuyaNagase MikiShinohara NatsukoHanzawa MayumiSakumoto MarimuNishino TakahiroMaenosono RyoichiKawachi AsukaMukohyama JunkoYano ShingoMuto TomoyaYoshimi Akihide - Basal pancreatic ductal adenocarcinoma (PDAC) has the worst overall survival and is the only subtype that serves as an independent poor prognostic factor. We identify elevated levels of LIN28B and its downstream target, HMGA2, in basal PDAC. Notably, LIN28B significantly accelerates KRAS-driven PDAC progression in a mouse model. Here, we show that HMGA2 promotes basal PDAC pathogenesis by enhancing mRNA translation downstream of LIN28B. Mechanistically, HMGA2 suppresses leucine carboxyl methyltransferase 1 (LCMT1) at the chromatin level, reducing PP2A methylation and activity. This leads to increased phosphorylation of S6K and eIF4B, boosting mRNA translation. Additionally, HMGA2 downregulates B56α (PPP2R5A), disrupting functional PP2A holoenzyme assembly and further sustaining phosphorylated S6K levels. Impaired PP2A function mimics HMGA2's effects, reinforcing increased mRNA translation and basal lineage features. This work uncovers a critical link between the LIN28B/HMGA2 axis, protein synthesis, and PDAC lineage specificity via LCMT1-mediated PP2A methylation and B56α-PP2A disruption. - Source: PubMed
Publication date: 2025/05/26
Dobersch StephanieYamamoto NaomiSchutter AidanCavender Sarah MRobertson Tess MKartha NithyaSamraj Annie NDoron BenPoole Lisa AWladyka Cynthia LZhang AmyJang Gun HoMahalingam Aswanth HBarreto GuillermoRaghavan SrivatsanNarla GouthamNotta FaiyazEisenman Robert NHsieh Andrew CKugel Sita