-
oa Interference of Zinc Chelation with Cancer Cell Proliferation
- الناشر: Hamad bin Khalifa University Press (HBKU Press)
- المصدر: Qatar Foundation Annual Research Forum Proceedings, Qatar Foundation Annual Research Forum Volume 2011 Issue 1, نوفمبر ٢٠١١, المجلد 2011, BMP23
ملخص
Cell division is a complex process tightly regulated by several classes of genes. Cancers occur primarily due to misregulation of this machinery, resulting in uncontrolled growth of cells. We recently showed that the transition metal chelator, TPEN, blocks entry into meiosis of Xenopus oocytes and targets a protein involved in cell cycle: Cdc25c. Cdc25c is a dual specificity phosphatase that plays crucial roles in cell cycle progression particularly during the G2-M transition of the cell cycle. Analysis of recombinant Cdc25c metal content revealed that Cdc25c is a Zn2+-binding metalloprotein (Lu Sun et al., 2005).
Based on these findings we hypothesize that Zn2+ is an important cofactor for Cdc25c to adopt the right conformation to recognize and interact with its substrate Cdc2. To test this hypothesis, we used Arabidopsis Cdc25c because the Zn coordinating residues have been identified in this protein. This analysis identified the following residues as potential Zn-coordinating residues: H420, C507, C513, H516, and H517. To test whether these residues coordinate Zn we have mutated them to Ala and are presently purifying the mutant and wild-type proteins as recombinant proteins to test their phosphatase activity and ability to induce entry into M-phase following microinjection into oocytes.