Ask about this productRelated genes to: PPP1R15B Blocking Peptide
- Gene:
- PPP1R15B NIH gene
- Name:
- protein phosphatase 1 regulatory subunit 15B
- Previous symbol:
- -
- Synonyms:
- FLJ14744
- Chromosome:
- 1q32.1
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-29
- Date modifiied:
- 2015-11-18
Related products to: PPP1R15B Blocking Peptide
Related articles to: PPP1R15B Blocking Peptide
- The integrated stress response (ISR) is essential for cellular homeostasis and cognitive function. We investigated how persistent ISR activation affects cognitive performance by studying the PPP1R15B genetic variant associated with intellectual disability. To model this condition, we generated a mouse line with the pathogenic allele inserted. This variant destabilized the PPP1R15B•PP1 phosphatase complex, causing persistent ISR activation, impaired protein synthesis, and long-term memory deficits. We demonstrated that the cognitive and synaptic impairments in mice arise directly from ISR activation. Furthermore, we characterized DP71L, a viral ortholog of PPP1R15B, which acted as a potent pan-ISR inhibitor. DP71L reversed the cognitive and synaptic deficits across mouse models of Down syndrome, Alzheimer's disease, and aging, and enhanced synaptic plasticity and memory in healthy mice. - Source: PubMed
Publication date: 2026/04/02
Reineke Lucas CZhu Ping JunDalwadi UditDooling Sean WLiu YuweiWang I-ChingYoung-Baird SaraOkoh JamesKuncha Santosh KumarZhou HongyiKannan AksharaPark HyekyungDebeaubien Nicolas ACroll TristanLee D JohnArthur ChristopherDever Thomas EWalter PeterChen JinFrost AdamCosta-Mattioli Mauro - Lenvatinib is a first-line therapy for advanced hepatocellular carcinoma (HCC), yet the emergence of lenvatinib-tolerant persister cells (LTPCs) contributes to therapeutic failure and tumor relapse. The molecular programs that sustain this tolerant state remain insufficiently defined. Here, we investigated the role of the PPP1R15B-ATF4 stress-response axis in mediating lenvatinib tolerance and ferroptosis resistance. - Source: PubMed
Publication date: 2026/01/08
Chen Ming-YaoLai Shiue-WeiCheng Yi-ChiaoYadav Vijesh KumarFong Iat-HangKuo Kuang-TaiLee Kuen-HaurCherng Yih-Giun - Secretory proteins are synthesized in the endoplasmic reticulum (ER) and begin their transport from specialized domains on the ER called ER exit sites (ERES), where COPII proteins assemble. We previously demonstrated that the interaction between TANGO1 and Sec16A is critical for ERES formation. In this study, we reveal that the phosphorylation of TANGO1 and Sec16A is regulated by a FAM83A/CK1α-mediated negative feedback loop. Conversely, their dephosphorylation is regulated in a spatially distinct manner by different phosphatase complexes: PPP6R3/PPP6C for Sec16A and PPP1R15B/PPP1C for TANGO1. Excessive phosphorylation of either TANGO1 or Sec16A leads to ERES disassembly, while excessive dephosphorylation impairs secretion. Our findings demonstrate that maintaining a balanced phosphorylation state of TANGO1 and Sec16A through autoregulation by FAM83A/CK1α and the phosphatases PP1 and PP6 is essential for sustaining proper secretory activity at the ERES. - Source: PubMed
Publication date: 2025/11/25
Maeda MiharuArakawa MasashiWakabayashi MasakiKomatsu YukieSaito Kota - Stress responses enable cells to detect, adapt to, and survive challenges. The benefit of these signaling pathways depends on their reversibility. The integrated stress response (ISR) is elicited by phosphorylation of eukaryotic translation initiation factor eIF2, which traps and inhibits rate-limiting translation factor eIF2B, thereby attenuating translation initiation. Termination of this pathway thus requires relieving eIF2B from P-eIF2 inhibition. Here, we found that eIF2 phosphatase subunits PPP1R15A and PPP1R15B (R15B) bound P-eIF2 in complex with eIF2B. Biochemical investigations guided by cryo-electron microscopy structures of native eIF2-eIF2B and P-eIF2-eIF2B complexes bound to R15B demonstrated that R15B enabled dephosphorylation of otherwise dephosphorylation-incompetent P-eIF2 on eIF2B. This sheds light on ISR termination, revealing that R15B rescues eIF2B from P-eIF2 inhibition, thereby safeguarding translation and cell fitness. - Source: PubMed
Publication date: 2026/02/19
De Miguel ClaudiaThorkelsson Sigurdur RFatalska AgnieszkaHodgson GeorgeDalglish MaximillianWang ChaoBertolotti Anne - The long non-coding RNA lnc-FANCI-2 acts as a host defense RNA and is highly expressed in HPV-positive cervical lesions. Its activation relies on the binding of the transcription factor YY1 to two conserved motifs in its promoter. We used DNA oligo pull-down combined with mass spectrometry to identify proteins binding to the lnc-FANCI-2 promoter, discovering new TFAP2 family members that compete with YY1 for binding at overlapping sites. In primary epithelial cells, TFAP2 binding led to lnc-FANCI-2 silencing. However, in HPV-positive cancer cells, increased YY1 levels displaced TFAP2, alleviating repression. Genome-wide predictions using the JASPAR database identified thousands of YY1 and TFAP2 competition binding sites (CBSs), many overlapping with CHIP-seq peaks for YY1, TFAP2A, and TFAP2C, predominantly in promoter regions. We validated competition at two CBSs in the promoter and found it likely regulates cancer-related genes PPP1R15B and LRRC37A. This suggests that YY1 and TFAP2 competition might influence a broader transcriptional regulation network in HPV-induced cancer. This study reveals a novel transcriptional antagonism mechanism affecting lnc-FANCI-2 and other cancer-related genes, highlighting YY1 and TFAP2 as potential therapeutic targets in HPV-driven carcinogenesis. - Source: PubMed
Publication date: 2025/09/15
Liu YiDing ShuangLiu Haibin