Ryo Kanazawa

Bio: Ryo Kanazawa is an academic researcher from Tohoku University. The author has contributed to research in topics: Centrosome & Rearrangement reaction. The author has an hindex of 3, co-authored 6 publications receiving 46 citations.

RACK1 regulates centriole duplication by controlling localization of BRCA1 to the centrosome in mammary tissue-derived cells

Abstract: Breast cancer gene 1 (BRCA1) is a tumor suppressor that is associated with hereditary breast and ovarian cancer. BRCA1 functions in DNA repair and centrosome regulation together with BRCA1-associated RING domain protein (BARD1), a heterodimer partner of BRCA1. Obg-like ATPase 1 (OLA1) was identified as a protein that interacts with BARD1. OLA1 regulates the centrosome by binding to and collaborating with BRCA1 and BARD1. We identified receptor for activated C kinase (RACK1) as a protein that interacts with OLA1. RACK1 directly bound to OLA1, the N-terminal region of BRCA1, and γ-tubulin, associated with BARD1, and localized the centrosomes throughout the cell cycle. Knockdown of RACK1 caused abnormal centrosomal localization of BRCA1 and abrogated centriole duplication. Overexpression of RACK1 increased the centrosomal localization of BRCA1 and caused centrosome amplification due to centriole overduplication. The number of centrioles in cells with two γ-tubulin spots was higher in cell lines derived from mammary tissue compared to those derived from other tissues. The effects of aberrant RACK1 expression level on centriole duplication were observed in cell lines derived from mammary tissue, but not in those derived from other tissues. Two BRCA1 variants, R133H and E143K, and a RACK1 variant, K280E, associated with cancer, which weakened the BRCA1-RACK1 interaction, interfered with the centrosomal localization of BRCA1 and reduced centrosome amplification induced by overexpression of RACK1. These results suggest that RACK1 regulates centriole duplication by controlling the centrosomal localization of BRCA1 in mammary tissue-derived cells and that this is dependent on the BRCA1-RACK1 interaction.

RACK1 regulates centriole duplication through the activation of polo-like kinase 1 by Aurora A.

Abstract: Breast cancer gene 1 (BRCA1) contributes to the regulation of centrosome number. We previously identified receptor for activated C kinase 1 (RACK1) as a BRCA1-interacting partner. RACK1, a scaffold protein that interacts with multiple proteins through its seven WD40 domains, directly binds to BRCA1 and localizes to centrosomes. RACK1 knockdown suppresses centriole duplication, whereas RACK1 overexpression causes centriole overduplication in a subset of mammary gland-derived cells. In this study, we showed that RACK1 binds directly to polo-like kinase 1 (PLK1) and Aurora A, and promotes the Aurora A/PLK1 interaction. RACK1 knockdown decreased phosphorylated PLK1 (p-PLK1) level and the centrosomal localization of Aurora A and p-PLK1 in S phase, whereas RACK1 overexpression increased p-PLK1 level and the centrosomal localization of Aurora A and p-PLK1 in interphase, resulting in an increase of cells with abnormal centriole disengagement. Overexpression of cancer-derived RACK1 variants failed to enhance the Aurora A/PLK1 interaction, PLK1 phosphorylation, and the centrosomal localization of p-PLK1. These results suggest that RACK1 functions as a scaffold protein for the activation of PLK1 by Aurora A to promote centriole duplication.

Efficient Synthesis of N-Alkylated α,β-Unsaturated Ketonitrones via Cu-Catalyzed Rearrangement.

Abstract: N-Alkylated unsaturated ketonitrones were efficiently synthesized from propargyloxyamines using Cu catalysts. Mechanistic studies suggest that the rearrangement reaction proceeds via Cu-catalyzed intramolecular hydroamination, followed by thermally induced electrocyclic ring opening.

Synthesis and Transformations of Nitrones for Organic Synthesis

Abstract: Nitrones are important compounds and are highly useful in many aspects. The first part describes the methods for synthesis of nitrones, which are useful and environmentally friendly. Catalytic oxidations, condensations, and other useful reactions are described. The nitrones thus obtained are key intermediates for the synthesis of biologically important nitrogen compounds. The second part describes the fundamental transformations of nitrones, which will provide the strategies and means for the construction of nitrogen compounds. The reactions with nucleophiles or radicals, C–H functionalization, and various addition reactions are described. The last reactions are particularly important for highly selective carbon—carbon bond formations. 1,3-Dipolar cycloaddition reactions are excluded because the size of the review is limited and excellent reviews have been published in Chemical Reviews.

New developments of ketonitrones in organic synthesis

Abstract: Nitrone chemistry has been widely developed for a long time and many reviews have outlined its rich transformation chemistry. However, most of these reviews involve aldonitrones due to their easy preparation and high reactivity. In recent years, N-substituents α,β-unsaturated ketonitrones and N-vinyl nitrones have attracted much attention of synthetic chemists to develop novel methodologies for their preparation and transformation. Various properties and new transformations of these nitrones have been discovered and applied into the synthesis of important heterocycle scaffolds. This review describes some recent breakthroughs in the development of new transformation of these nitrones. These new reactions include novel strategies for preparation of N-substituents α,β-unsaturated ketonitrones or N-vinyl nitrones, new rearrangement of nitrones, and reaction of nitrones with dipolarophiles such as alkynes, allenes and isocyanates.