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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gao, Yuan Zhou, Jie Kuang, Yi Xu, Chen Shi, Junfeng Xu, Bing Long, Marcus J. C. Hedstrom, Lizbeth |
| Description | Author Affiliation: Kuang Y ( From the Department of Chemistry.); Long MJ ( Graduate Program in Biochemistry and Biophysics.); Zhou J ( From the Department of Chemistry.); Shi J ( From the Department of Chemistry.); Gao Y ( From the Department of Chemistry.); Xu C ( Rosenstiel Basic Medical Sciences Research Center, and.); Hedstrom L ( From the Department of Chemistry, Department of Biology, Brandeis University, Waltham, Massachusetts 02454.); Xu B ( From the Department of Chemistry, bxu@brandeis.edu.) |
| Abstract | Emerging evidence reveals that prion-like structures play important roles to maintain the well-being of cells. Although self-assembly of small molecules also affords prion-like nanofibrils (PriSM), little is known about the functions and mechanisms of PriSM. Previous works demonstrated that PriSM formed by a dipeptide derivative selectively inhibiting the growth of glioblastoma cells over neuronal cells and effectively inhibiting xenograft tumor in animal models. Here we examine the protein targets, the internalization, and the cytotoxicity pathway of the PriSM. The results show that the PriSM selectively accumulate in cancer cells via macropinocytosis to impede the dynamics of cytoskeletal filaments via promiscuous interactions with cytoskeletal proteins, thus inducing apoptosis. Intriguingly, Tau proteins are able to alleviate the effect of the PriSM, thus protecting neuronal cells. This work illustrates PriSM as a new paradigm for developing polypharmacological agents that promiscuously interact with multiple proteins yet result in a primary phenotype, such as cancer inhibition. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 42 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-10-17 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cytoskeleton Metabolism Nanoparticles Chemistry Neoplasms Prions Antineoplastic Agents Apoptosis Endocytosis Glioblastoma Drug Therapy HeLa Cells Hep G2 Cells MCF-7 Cells Nanotechnology Neoplasm Transplantation Nocodazole Paclitaxel Peptides Protein Structure, Tertiary Tubulin Tau Proteins Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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