EF hand (EFh) domain-containing proteins have been implicated in malignant progression, but their precise functional contributions are uncertain. Here, we report evidence that the EFh protein IBA2 promotes the proliferation of breast cancer cells by facilitating their transit through the G1-S cell-cycle transition. Mechanistic investigations revealed that IBA2 acted at the transcriptional level to promote the expression of the critical cell-cycle regulator cyclin D1. Clinically, we found that levels of IBA2 were significantly upregulated in breast cancer specimens, where its expression correlated positively with histologic grade. Our results suggest a key role for IBA2 in mammary tumorigenesis. Cancer Res; 76(15); 4535-45. ©2016 AACR.
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Article Synopsis
- The study examines Iba2, a protein similar to Iba1, focusing on its structure, ability to bind and cross-link actin, and the way it behaves in cells during bacterial invasion.
- Iba2 has a unique crystal structure characterized by two EF-hand motifs and forms homodimers that are stabilized by disulfide bridges and zinc ions, but it does not bind calcium effectively like Iba1.
- Both Iba1 and Iba2 show similar F-actin binding and cross-linking activities; however, Iba1 tends to localize more prominently in cellular projections during bacterial infections compared to Iba2.
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