DAB2IP and Chromosome Stability

Defects in kinetochore-microtubule (KT-MT) attachment and the spindle assembly checkpoint (SAC) during cell division are strongly associated with chromosomal instability. Chromosomal instability has been linked to carcinogenesis, metastasis, poor prognosis, and resistance to cancer therapy.

We previously reported that the DAB2IP (DOC-2/DAB2 Interacting Protein) is a tumor suppressor and that loss of DAB2IP is often detected in advanced prostate cancer and is indicative of poor prognosis. Our lab discovered that the loss of DAB2IP results in impaired KT-MT attachment, compromised SAC, and aberrant chromosomal segregation.

We found that DAB2IP directly interacts with Plk1, and its loss inhibits Plk1 kinase activity, thereby impairing Plk1-mediated BubR1 phosphorylation. Loss of DAB2IP decreases the localization of BubR1 at the kinetochore during mitosis progression, leading to tumorigenesis and resistance to chemotherapy.

Our findings demonstrate a novel function of DAB2IP in the maintenance of KT-MT structure and SAC regulation during mitosis, which is essential for chromosomal stability.