Tankyrase 1 regulates centrosome function by controlling CPAP stability

Abstract CPAP—a gene mutated in primary microcephaly—is required for procentriole formation. Here we show that CPAP degradation and function is controlled by the poly(ADP‐ribose) polymerase tankyrase 1. CPAP is PARsylated by tankyrase 1 in vitro and in vivo. Overexpression of tankyrase 1 leads to CP...
Ausführliche Beschreibung

Abstract CPAP—a gene mutated in primary microcephaly—is required for procentriole formation. Here we show that CPAP degradation and function is controlled by the poly(ADP‐ribose) polymerase tankyrase 1. CPAP is PARsylated by tankyrase 1 in vitro and in vivo. Overexpression of tankyrase 1 leads to CPAP proteasomal degradation, preventing centriole duplication, whereas depletion of tankyrase 1 stabilizes CPAP in G1, generating elongated procentrioles and multipolarity. Tankyrase 1 localizes to centrosomes exclusively in G1, coinciding with CPAP degradation. Hence, tankyrase 1‐mediated PARsylation regulates CPAP levels during the cell cycle to limit centriole elongation and ensure normal centrosome function. Ausführliche Beschreibung