Structural and functional analyses of minimal phosphopeptides targeting the polo-box domain of polo-like kinase 1

Polo-like kinase-1 (Plk1) has a pivotal role in cell proliferation and is considered a potential target for anticancer therapy. The noncatalytic polo-box domain (PBD) of Plk1 forms a phosphoepitope binding module for protein-protein interaction. Here, we report the identification of minimal phosphopeptides that specifically interact with the PBD of human PLK1, but not those of the closely related PLK2 and PLK3. Comparative binding studies and analyses of crystal structures of the PLK1 PBD in complex with the minimal phosphopeptides revealed that the C-terminal SpT dipeptide functions as a high-affinity anchor, whereas the N-terminal residues are crucial for providing specificity and affinity to the interaction. Inhibition of the PLK1 PBD by phosphothreonine mimetic peptides was sufficient to induce mitotic arrest and apoptotic cell death. The mode of interaction between the minimal peptide and PBD may provide a template for designing therapeutic agents that target PLK1.National Institutes of Health (U.S.) (Grant R01 GM60594)National Cancer Institute (U.S.)National Institutes of Health (U.S.) (Contract N01-CO-12400)National Institutes of Health (U.S.) (HHSN261200800001E

A dermatologic assessment of 101 mpox (monkeypox) cases from 13 countries during the 2022 outbreak: skin lesion morphology, clinical course, and scarring

BACKGROUND: In the 2022 monkeypox (mpox) outbreak, 79,000 global cases have been reported. Yet, limited dermatologic data have been published regarding lesion morphology and progression. OBJECTIVE: To characterize skin lesion morphology, symptomatology, and outcomes of mpox infection over time. METHODS: The AAD/ILDS Dermatology COVID-19, Monkeypox, and Emerging Infections Registry captured de-identified patient cases of mpox entered by healthcare professionals. RESULTS: From August 4-November 13 2022, 101 cases from 13 countries were entered, primarily by dermatologists (92%). Thirty-nine percent had fewer than five lesions. In 54% of cases skin lesions were the first sign of infection. In the first 1-5 days of infection, papules (36%), vesicles (17%) and pustules (20%) predominated. By days 6-10, pustules (36%) were most common, followed by erosions/ulcers (27%) and crusts/scabs (24%). Crusts/scabs were the predominant morphology after Day 11. Ten cases of morbilliform rash were reported. Scarring occurred in 13% of cases. LIMITATIONS: Registry-reported data cannot address incidence. There is potential reporting bias from the predilection to report cases with greater clinical severity. DISCUSSION: These findings highlight differences in skin findings compared to historical outbreaks, notably the presence of skin lesions prior to systemic symptoms and low overall lesion-counts. Scarring emerged as a major possible sequela

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

non present