University of Kentucky
Finding the Missing Link Between Autophagy and Cell Growth Control - a Novel Target for Treating Cancer?
Institution
University of Kentucky
Faculty Advisor/ Mentor
Qingjun Wang
Abstract
One of the most life-threatening diseases that plagues human beings today is cancer. Autophagy is a cellular degradation pathway that is essential for the removal and degradation of unnecessary and damaged organelles along with proteins in time of stress and starvation. Autophagy impairment can lead to unregulated cell division and unrestrained cell growth characteristics of cancer. Beclin 1 is a critical regulator of autophagy. Partial deletion of Beclin1 leads to increased incidence of tumors, and total deletion of Beclin1 leads to death in mice at the embryonic stage. This study examined the role of a novel Beclin 1-interacting protein, p40, in cell division and proliferation. We showed that transient knockdown of p40 increases cell proliferation. We have also shown that p40 co-localizes with the key cell division protein γ-tubulin on centrosome, suggesting that p40 is involved in cell division. We hypothesized that autophagy may directly regulate cell division via p40 at the centrosome. We further hypothesized that alteration of p40- Beclin1 or p40-γ-tubulin interaction can lead to increased cell proliferation. We have generated a series of DNA constructs encoding either full length or truncated p40. Using these constructs and a variety of protein-protein interaction and cell growth assays, we characterized the protein domain(s) of p40 that interact with Beclin1 and colocalize with γ-tubulin. Furthermore, we also studied whether disrupting these protein-protein interaction domains in p40 leads to impaired starvation-induced cell proliferation inhibition. This study has shed light on our understanding of cancer and our adventure towards effective cancer treatment.
Finding the Missing Link Between Autophagy and Cell Growth Control - a Novel Target for Treating Cancer?
One of the most life-threatening diseases that plagues human beings today is cancer. Autophagy is a cellular degradation pathway that is essential for the removal and degradation of unnecessary and damaged organelles along with proteins in time of stress and starvation. Autophagy impairment can lead to unregulated cell division and unrestrained cell growth characteristics of cancer. Beclin 1 is a critical regulator of autophagy. Partial deletion of Beclin1 leads to increased incidence of tumors, and total deletion of Beclin1 leads to death in mice at the embryonic stage. This study examined the role of a novel Beclin 1-interacting protein, p40, in cell division and proliferation. We showed that transient knockdown of p40 increases cell proliferation. We have also shown that p40 co-localizes with the key cell division protein γ-tubulin on centrosome, suggesting that p40 is involved in cell division. We hypothesized that autophagy may directly regulate cell division via p40 at the centrosome. We further hypothesized that alteration of p40- Beclin1 or p40-γ-tubulin interaction can lead to increased cell proliferation. We have generated a series of DNA constructs encoding either full length or truncated p40. Using these constructs and a variety of protein-protein interaction and cell growth assays, we characterized the protein domain(s) of p40 that interact with Beclin1 and colocalize with γ-tubulin. Furthermore, we also studied whether disrupting these protein-protein interaction domains in p40 leads to impaired starvation-induced cell proliferation inhibition. This study has shed light on our understanding of cancer and our adventure towards effective cancer treatment.