Tankyrase 1 regulates centrosome function by controlling CPAP stability.
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.
Molecular Pathogenesis Program and Department of Pathology, Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Mi Kyung
MK
Kim
Charles
C
Dudognon
Susan
S
Smith
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism*; D016193:G1 Phase; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011485:Protein Binding; D055550:Protein Stability; D059748:Proteolysis; D038501:Tankyrases / Q000378:metabolism*; D054875:Ubiquitination
D008869:Microtubule-Associated Proteins; D011065:Poly(ADP-ribose) Polymerases; D038501:Tankyrases; C414735:CENPJ protein, human; C418109:TNKS protein, human