Ask about this productRelated genes to: PPP3CA Blocking Peptide
- Gene:
- PPP3CA NIH gene
- Name:
- protein phosphatase 3 catalytic subunit alpha
- Previous symbol:
- CALN, CALNA
- Synonyms:
- CNA1, PPP2B
- Chromosome:
- 4q24
- Locus Type:
- gene with protein product
- Date approved:
- 1990-06-26
- Date modifiied:
- 2016-02-10
Related products to: PPP3CA Blocking Peptide
Related articles to: PPP3CA Blocking Peptide
- Infants and children with KMT2A::AFF1+ leukemia have a dismal prognosis and are therefore in urgent need for more efficient and less aggressive therapy. In this study, we investigated three microRNAs that are downregulated in KMT2A::AFF1+ B-cell precursor acute lymphoblastic leukemia (BCP-ALL): miR-194, miR-99b, and miR-125a-5p. When overexpressed, all three microRNAs impaired the survival of KMT2A::AFF1+ leukemic blasts and the maintenance of KMT2A::AFF1+ BCP-ALL. We identified microRNA target genes responsible for this phenotype that are upregulated in KMT2A::AFF1+ BCP-ALL: CA5B, PPP3CA, and PPP2R5C. Importantly, using a drug-repurposing approach, we found that inhibition of CA5B, PPP3CA, and PP2A by acetazolamide, tacrolimus, and LB-100, respectively, showed high toxicity toward KMT2A::AFF1+ leukemic blasts and reduced leukemia burden in vivo. Furthermore, acetazolamide was able to prolong the survival of patient-derived xenotransplant models in combination with infant ALL induction therapy. This study highlights how the unique microRNA expression signature of patients with KMT2A::AFF1+ BCP-ALL can be used to uncover novel therapeutic avenues and accelerate drug repurposing. It also indicates potential new drug combinations for less toxic chemotherapy. - Source: PubMed
Publication date: 2026/04/23
Malouf CamilleDuguid AlasdairVrenken Kirsten SLeah TomMedhi RaginiCamiolo GiuseppinaNitsche LeslieJakobczyk HélèneKotecha Rishi SAnderson Richard ABarrett Neil ASmith Owen PStam Ronald WOttersbach Katrin - - Source: PubMed
Publication date: 2026/04/09
Contrucci Bruno AntunesThomé UrsulaBatista Larissa AparecidaLorenzoni Ana Laura Volpi MartinsCaldas Carla Andrea Cardoso TanuriSakamoto Americo CeikiGomy IsraelBatista Lisandra Mesquitade Almeida Marcela LopesHamad Ana Paula AndradeTraslaviña Guillermo Andrey Ariza - Proteins with incomplete functional characterization represent a major opportunity to uncover novel mechanisms underlying tumor progression. C20orf112 (also known as NOL4L) has been implicated in tumor biology, yet its regulatory mechanisms and role in colorectal cancer (CRC) remain largely undefined. Here, using a sphere formation-colony formation swapping culture model, we identified C20orf112 as a potent regulator of CRC stemness and elucidated its underlying mechanism. Immunohistochemical (IHC) analysis revealed that C20orf112 is significantly overexpressed in CRC tissues compared with adjacent noncancerous tissues. Functional studies demonstrated that C20orf112 enhances cancer stemness in CRC by activating ERK signaling. Mechanistically, C20orf112 is dephosphorylated at serine 295 (S295) by the phosphatase complex PPP3CA/PPIA, promoting its nuclear translocation. This dephosphorylation increases the binding affinity between C20orf112 and karyopherin KPNA2, facilitating nuclear import. Subsequent nuclear accumulation of C20orf112 is associated with sustained ERK activation and promotes a stem-like phenotype. Collectively, these findings reveal a previously unrecognized PPP3CA/PPIA-KPNA2-ERK signaling axis that regulates C20orf112 function in CRC, highlighting its context-specific regulatory role and therapeutic potential. - Source: PubMed
Publication date: 2026/03/30
Wang Xiao-XuanPan En-GuangZeng Yong-HuiGao Gui-BinWang Wan-NanHuang Rui-HuaFan Zi-HongZhong Jian-RuiZheng Yan-ShengHe Qing-YuWang YangZhang Jing - We previously reported that transcription factor EB (TFEB) plays a crucial role in regulating the ischemic stroke (IS)-mediated dynamic changes of autophagic flux. Protein phosphatase 3 (PPP3) may regulate the transcriptional activity of TFEB. However, the main isoform of the PPP3 catalytic subunit (PPP3C) involved in TFEB activation, the PPP3-binding site in TFEB, and the upstream regulatory mechanism of PPP3 activation after cerebral ischemia are still unknown. Here, we show that the interaction between TFEB and PPP3 catalytic subunit B (PPP3CB), but not PPP3CA, is strengthened after IS. Knockdown of PPP3CB, but not PPP3CA, significantly inhibited the oxygen glucose deprivation (OGD)-induced increase in the transcriptional activity of TFEB, blocked autophagic flux, and exacerbated neuronal death. Furthermore, the YLAVP peptide, which blocks the LxVP motif-binding site of PPP3C, repressed TFEB transcriptional activity and autophagic flux, and exacerbated neuronal death after OGD. Treatment with ML-SI1, which inhibits the lysosomal calcium channel MCOLN1, blocked the OGD-induced enhancement of TFEB transcriptional activity and autophagic flux, and further aggravated neuronal death. These effects were partly reversed by the MCOLN1 agonist ML-SA1. The PPP3 inhibitor cyclosporin A (CsA) abolished the ML-SA1-induced TFEB transcriptional activation and reduced neuronal death. Our findings identify for the first time that MCOLN1-mediated-PPP3CB activation alleviates neuronal damage by promoting TFEB-dependent autophagic flux in permanent cerebral ischemia. The LxVP motif is required for the interaction between PPP3 and TFEB in response to OGD. This study provides an in-depth insight into the mechanisms underlying TFEB-mediated activation of autophagic flux following IS. Schematic diagram showing how MCOLN1-mediated activation of PPP3CB reduces neuronal damage by promoting TFEB-dependent autophagic flux in permanent cerebral ischemia. - Source: PubMed
Publication date: 2026/03/24
Liu Shi-QiLiu Yue-YangFu Xiao-XiaoCui Pei-RuiWang XinWang Sai-QianWu Chun-FuWang Li-HuiLuo JingYang Jing-Yu - Recently, de novo heterozygous variants of Calcineurin (CN) were reported as the cause of a neurodevelopmental disorder that presents with epileptic encephalopathy and dysmorphism (DEE91), with the largest group of patients harboring the CN missense mutation E282K (glutamate → lysine). Here, we use molecular and cellular techniques to define how this mutation alters CN activity. We discover that basophilic substrates use an arginine residue to bind to CN via an acidic substrate recruitment pocket adjacent to the CN active site, the E282 pocket. Furthermore, we show that basic residues in the i-1 position of the substrate relative to the substrate phosphosite enhance CN-mediated dephosphorylation. While the CN structure shows that the overall conformation is unchanged, the E282 pocket transforms from acidic to basic, with pocket access blocked by the formation of a E282K-E237 salt bridge. Finally, in vitro assays and in cell phosphoproteomics show that CN shifts CN substrate dephosphorylation profiles from basic to acidic, thereby altering CN-mediated dephosphorylation signaling. Together, these data define the molecular impact of the CN variant in cells and development, providing a key step for developing strategies to treat this disorder and its accompanying complications. - Source: PubMed
Publication date: 2026/02/16
Shirakawa Karina TParikh TveshaMachado Luciana E S FPoimenidou GaliniNguyen Hieu TDell'Acqua Mark LKettenbach Arminja NPage RebeccaPeti Wolfgang