Autophagy could be non-selective or selective. In selective autophagy, autophagosome recruits its cargoes through protein interaction with membrane receptor LC3/Atg8. Through a proteomics approach, we identified OFD1 (oral-facial-digital syndrome 1) protein as a substrate of autophagy. OFD1 interacts with LC3 at centriolar satellites, whereas it functions as a suppressor of primary ciliogenesis. OFD1 suppression is removed by autophagy upon serum starvation, a condition that strongly promotes ciliogenesis. Forced reduction of OFD1 by shRNA induces primary cilia formation in mouse embryonic fibroblasts and human breast cancer MCF7 cells. Surprisingly, MCF7 cells is generally considered a non-ciliary cells doe to complete lack of cilia. We can turn this non-ciliary cell to cilia-competent cell by only changing single protein factor. The identification of this key suppressive mechanism brings hope to the therapy of ciliopathy and certain cancers those are believed to be caused by ciliary defects. We are actively studying the underlying mechanism and will screen chemical compounds to target this pathway.
- Tang Z, Lin MG, Stowe TR, Chen S, Zhu M, Stearns T, Franco B, Zhong Q. Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites. Nature, 2013, Oct 2;502, 254-257.