Significance Found in most eukaryotic cells, a centriole is a cylindrically shaped subcellular structure that plays an important role in various cellular processes, including mitotic spindle formation and chromosome segregation. Centriole duplication occurs only once per cell cycle, thus ensuring accurate control of centriole numbers to maintain genomic integrity. Although a growing body of evidence suggests that a Ser/Thr protein kinase, polo-like kinase 4 (Plk4), is a key regulator of centriole duplication, how Plk4 is recruited to centrosomes remains largely unknown. Here we showed that Plk4 dynamically localizes to distinct subcentrosomal regions by interacting with two hierarchically regulated scaffolds, Cep192 and Cep152. Highlighting the importance of these interactions, mutational disruption of either one of these interactions was sufficient to cripple Plk4-dependent centriole biogenesis.

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Polo-like kinase 4 (Plk4) is a key regulator of centriole duplication, an event critical for the maintenance of genomic integrity. Here we showed that Plk4 relocalizes from the inner Cep192 ring to the outer Cep152 ring as newly recruited Cep152 assembles around the Cep192-encircled daughter centriole. Crystal structure analyses revealed that Cep192 - and Cep152-derived peptides bind the cryptic polo box (CPB) of Plk4 in opposite orientations and in a mutually exclusive manner. The Cep152-peptide bound to the CPB markedly better than the Cep192-peptide and effectively snatched the CPB away from a preformed CPB–Cep192-peptide complex. A cancer-associated Cep152 mutation impairing the Plk4 interaction induced defects in procentriole assembly and chromosome segregation. Thus, Plk4 is intricately regulated in time and space through ordered interactions with two distinct scaffolds, Cep192 and Cep152, and a failure in this process may lead to human cancer.

Propolis is a resinous substance collected by honeybees from various plant sources. The composition of propolis depends on time, vegetation, and the area of collection. This study examined the antioxidant activity of propolis from various areas of Korea: Chilgok, Cheongju, Geochang, Muju, Pocheon, and Sangju. Ethanol extracts of propolis (EEP) were prepared and evaluated for their antioxidant activity by beta-carotene bleaching, 1,1-diphenyl-2-picrylhydrazyl free radical scavenging, and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation decolorization assays. Furthermore, the major constituents in EEP were identified by high-performance liquid chromatography analysis with a photodiode array and mass spectrometric detection, and each component was quantitatively analyzed. EEP from Cheongju and Muju had relatively strong antioxidant activity accompanied by high total polyphenol contents. Propolis from Cheongju contained large amounts of antioxidative compounds, such as caffeic acid, kaempferol, and phenethyl caffeate. On the other hand, propolis from Pocheon had compounds not seen in propolis from other areas.

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Propolis possesses various physiological activities. In this study, we examined the antiangiogenic and antioxidant activities of various components from propolis: acacetin, apigenin, artepillin C, caffeic acid phenethyl ester, chrysin, p-coumaric acid, galangin, kaempferol, pinocembrin, and quercetin. The effects of these components were tested on in vitro models of angiogenesis, tube formation and growth of human umbilical vein endothelial cells (HUVECs). Furthermore, these components were evaluated for their antioxidant activities by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging and ferric reducing/antioxidant power (FRAP) assays. Two propolis components, caffeic acid phenethyl ester, and quercetin, possessed strong inhibitory effects on tube formation and on endothelial cell proliferation and, coincidentally, showed strong antioxidant activity. Artepillin C, galangin, and kaempferol also possessed strong antiangiogenic and antioxidant activities to a slightly less degree. In contrast, acacetin, apigenin, and pinocembrin possessed a considerable degree of antiangiogenic activities, although they showed very low antioxidant activities. From these results, we propose that components from propolis such as artepillin C, caffeic acid phenethyl ester, galangin, kaempferol, and quercetin might represent a new class of dietary-derived antioxidative compounds with antiangiogenic activities. These propolis components may have the potential to be developed into pharmaceutical drugs for the treatment of angiogenesis-dependent human diseases such as tumors.

Propolis is a natural resinous product collected by honeybees from certain plants. It has gained popularity as a food and alternative medicine. Poplar and Baccharis are well known as the source plants of European and Brazilian propolis, respectively. However, the propolis from Okinawa, Japan, contains some prenylflavonoids not seen in other regions such as Europe and Brazil, suggesting that the plant origin of Okinawan propolis is a particular plant that grows in Okinawa. To identify the plant origin of Okinawan propolis, we observed the behavior of honeybees as they collected material from plants and caulked it inside the hive. Honeybees scraped resinous material from the surface of plant fruits of Macaranga tanarius and brought it back to their hive to use it as propolis. We collected samples of the plant and propolis, and compared their constituents by high-performance liquid chromatography with a photo-diode array detector. We also compared their 1,1-diphenyl-2-picryl-hydrazyl radical scavenging activity. The chemical constituents and biological activity of the ethanol extracts of the plant did not differ from those of propolis. This indicates directly that the plant origin of Okinawan propolis is M. tanarius.

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