Id1 induces centrosome abnormalities, polyploidy and disrupts microtubule integrity

Abstract

Elevated expression of the helix-loop-helix protein, Inhibitor of Differentiation (Id1), is common in human cancer and is associated with tumour progression. Id1 has a well-defined role to dimerize with differentiation-specific basic HLH factors to regulate their transcriptional activities. Recently, it has been shown to co-localize and interact with centrosomes at interphase and mitosis suggesting a role in tumour progression through interfering with centrosome homeostasis. We report here that overexpression of Id1 induces multiple mitotic defects in cells characterized by increases in centrosome numbers, multipolar spindles, mono-astral spindles, distorted microtubules. Long term expression of Id1 induced aneuploidy and polyploidy in a telomerase immortalized nasopharyangeal epithelial cell line. These abnormal phenotypes overlaps with the mitotic defects induced by overexpression of Aurora kinase A, a crucial regulator of mitosis. We reported for the first time that Id1 could induces Aurora A expression. NF-κB activation is involved in Id1 induced Aurora A expression. Suppression of expression of Id1 or overexpression of Aurora A could rescue centrosome homeostasis and restore microtubule integrity. These observations support a role of Id1 in centrosome homeostasis and microtubule integrity; and contribute to chromosome instability in premalignant cells where Id1 is often overexpressed and facilitate their transformation into malignant cells.