CEP44 is required for maintaining centriole duplication and spindle integrity

Abstract

AbstractIn animal cells, the centrosome, consisting of two centrioles, duplicates only once per cell cycle for bipolar spindle formation. Defective centriole duplication results in abnormal spindle formation and chromosome missegregation, which is closely linked to tumor growth. However, the molecular mechanisms licensing only one centriole duplication cycle within a cell cycle are less well known. Here we found that CEP44 is negatively correlated with breast carcinoma. CEP44, jointly with CEP57 and CEP57L1, maintains centriole engagement in the interphase to ensure centriole duplication once per cell cycle. Depletion of CEP44 leads to centriole overduplication because of premature centriole disengagement and multipolar spindle formation. Additionally, CEP44 is phosphorylated by Aurora A at the G2/M phase to facilitate spindle localization and maintain spindle integrity. Collectively, our results reveal the function of CEP44 in spindle formation by preventing centriole overduplication and maintaining spindle integrity, and CEP44 may serve as a potential marker for breast carcinoma prognosis.