A5063919203- Cervical Cancer and HPV Research
- Endoplasmic Reticulum Stress and Disease
- RNA Research and Splicing
- RNA regulation and disease
- Glycosylation and Glycoproteins Research
- Chemical Synthesis and Analysis
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Platelet Disorders and Treatments
- Peptidase Inhibition and Analysis
- Hepatitis B Virus Studies
- Chronic Lymphocytic Leukemia Research
- Ubiquitin and proteasome pathways
- Pancreatic function and diabetes
- Bacterial biofilms and quorum sensing
- Biochemical and Molecular Research
- Antimicrobial Peptides and Activities
- Protein Tyrosine Phosphatases
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- bioluminescence and chemiluminescence research
- Biotin and Related Studies
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Pharmacological Effects of Natural Compounds
- Growth Hormone and Insulin-like Growth Factors
Enzo Life Sciences (United States)
2023-2024
Abstract Human papillomavirus (HPV) is a significant contributor to the global cancer burden, and its carcinogenic activity facilitated in part by HPV early protein 6 (E6), which interacts with E3-ligase E6AP, also known as UBE3A, promote degradation of tumor suppressor, p53. In this study, we present single-particle cryoEM structure full-length E6AP complex HPV16 E6 (16E6) p53, determined at resolution ~3.3 Å. Our reveals extensive protein-protein interactions between 16E6 explaining their...
Human papillomavirus (HPV) infections account for nearly all cervical cancer cases, which is the fourth most common in women worldwide. High-risk variants, including HPV16, drive tumorigenesis part by promoting degradation of tumor suppressor p53. This mediated HPV early protein 6 (E6), recruits E3 ubiquitin ligase E6AP and redirects its activity towards ubiquitinating Targeting interaction interface between E6 a promising modality to mitigate HPV-mediated In this study, we designed covalent...
Abstract Insulin-like growth factor (IGF) signaling is highly conserved and tightly regulated by proteases including Pregnancy-Associated Plasma Protein A (PAPP-A). PAPP-A its paralog PAPP-A2 are metalloproteases that mediate IGF bioavailability through cleavage of binding proteins (IGFBPs). Here, we present single-particle cryo-EM structures the catalytically inactive mutant (E483A) in complex with a peptide from substrate IGFBP5 (PAPP-A BP5 ) also substrate-free form, leveraging power...
Dephosphorylation of pSer51 the α subunit translation initiation factor 2 (eIF2α P ) terminates signaling in integrated stress response (ISR). A trimeric mammalian holophosphatase comprised a protein phosphatase 1 (PP1) catalytic subunit, conserved C-terminally located ~70 amino acid core substrate-specific regulatory (PPP1R15A/GADD34 or PPP1R15B/CReP) and G-actin (an essential cofactor) efficiently dephosphorylate eIF2α vitro. Unlike their viral invertebrate counterparts, with whom they...
PTPN2 (protein tyrosine phosphatase non-receptor type 2, or TC-PTP) and PTPN1 are attractive immuno-oncology targets, with the deletion of Ptpn1 Ptpn2 improving response to immunotherapy in disease models. Targeted protein degradation has emerged as a promising approach drug challenging targets including phosphatases. We developed potent PTPN2/N1 dual heterobifunctional degraders (Cmpd-1 Cmpd-2) which facilitate efficient complex assembly E3 ubiquitin ligase CRL4CRBN, mediate cells mice. To...
Myeloproliferative leukemia protein (MPL), also known as thrombopoietin (TPO) receptor, is a class I cytokine receptor that expressed on hematopoietic progenitors, promoting growth and differentiation toward the megakaryocyte lineage critical for normal platelet production. Mutations in MPL, TPO, or Janus kinase 2 (JAK2) have been implicated multiple diseases from congenital thrombocytopenias to myeloproliferative neoplasms. The ligand stimulates production by inducing MPL dimerization...
Covalent peptide binders have found applications as activity-based probes and irreversible therapeutic inhibitors. Currently, there is no rapid, label-free, tunable affinity selection platform to enrich covalent reactive from synthetic libraries. We address this challenge by developing a reversibly termed ReAct-ASMS enabled tandem high-resolution mass spectrometry (MS/MS) identify native protein targets. It uses mixed disulfide-containing peptides build reversible peptide-protein conjugates...
Abstract Pregnancy-Associated Plasma Protein A isoforms, PAPP-A and PAPP-A2, are metalloproteases that cleave insulin-like growth factor binding proteins (IGFBPs) to modulate signaling. The structures of homodimeric in complex with IGFBP5 anchor peptide, inhibitor STC2 proMBP have been recently reported. Here, we present the single-particle cryo-EM structure monomeric, N-terminal LG, MP, M1 domains (with exception LNR1/2) human PAPP-A2 3.13 Å resolution. Our together functional studies...
Covalent peptides have found widespread applications as activity-based probes and irreversible therapeutic inhibitors. Currently, there is no rapid, label-free, highly tunable affinity selection method to enrich covalent reactive from synthetic libraries. We address this challenge by developing a reversibly platform enabled tandem high resolution mass spectrometry (MS/MS) identify peptide binders native protein targets. It uses mixed disulfides build reversible peptide-protein conjugates...
ABSTRACT Human papillomavirus (HPV) infections account for nearly all cervical cancer cases, which is the fourth most common in women worldwide. High-risk variants, including HPV16, drive tumorigenesis part by promoting degradation of tumor suppressor p53. This mediated HPV early protein 6 (E6), recruits E3 ubiquitin ligase E6AP and redirects its activity towards ubiquitinating Targeting interaction interface between E6 a promising modality to mitigate HPV-mediated In this study, we designed...
Abstract Dephosphorylation of pSer51 the α subunit translation initiation factor 2 (eIF2α P ) terminates signalling in integrated stress response (ISR). A trimeric mammalian holophosphatase comprised a PP1 catalytic subunit, conserved C-terminally located ∼70 amino acid core substrate-specific regulatory (PPP1R15A/GADD34 or PPP1R15B/CReP) and G-actin (an essential co-factor) efficiently dephosphorylate eIF2α vitro. Unlike their viral invertebrate counterparts, with whom they share 70 residue...