Penn Medicine
   
 

Tim J. Yen, Ph.D.

The Pennsylvania Muscle Institute

Contact Information

Institute for Cancer Research
Fox Chase Cancer Center
7701 Burholme Ave.
Philadelphia, PA 19111
Phone: (215) 728-2590
Fax: (215) 728-3616
E-mail: yen@ew462.xsome.fccc.edu
Position: Member

Expertise

Our laboratory is interested in the mechanisms of microtubule-based motility- the directed motility of vesicles, organelles, and chromosomes along the microtubule cytoskeleton. Our research focuses on understanding the cellular role and function of cytoplasmic dynein, and its required activator dynactin. Dynactin is a unique oligomeric complex which binds to microtubules, to cytoplasmic dynein, and to spectrin via a filament formed from an actin-related protein. In Drosophila, both dynein and dynactin are essential: we are currently examining the roles of these proteins in vesicle trafficking in cells, including the rapid microtubule-based transport required in the extended axons of neuronal cells.

Representative Publications

  1. Gay, D. A., Yen, T. J., Lau, J. T. Y., Cleveland, D. W. (1987) Sequences that confer b-tubulin autoregulation through modulated mRNA stability reside with Exon 1 of b-tubulin mRNA. Cell 50:671-679.
  2. Joshi, H. C., Yen, T. J., Cleveland, D. W. (1987) In vivo coassembly of a divergent b-tubulin subunit (cb6) into microtubules of different function. J. Cell Biol. 105:2179-2190.
  3. Pachter, J. S., Yen, T. J., Cleveland, D. W. (1987) Autoregulation of tubulin is achieved through specific degradation of polysomal tubulin mRNAs. Cell 51:283-292.
  4. Yen, T. J., Gay, D. A., Pachter, J. S., Cleveland, D. W. (1988) Autoregulated changes in stability of polyribosome-bound b-tubulin mRNAs are specified by the first 13 translated nucleotides. Mol. Cell. Biol. 8:1224-1235.
  5. Yen, T. J., Machlin, P. S., Cleveland, D. W. (1988) Autoregulated instability of polysome-bound b-tubulin mRNAs is achieved through recognition of the nascent amino-terminus of tubulin. Nature 334: 580-585.
  6. Gabriel, A., Yen, T. J., Schwartz, D. C., Smith, C. L., Boeke, J. D., Sollner-Webb, B., Cleveland, D. W. (1990) A rapidly rearranging retrotransposon within the miniexon gene locus of Crithidia fasciculata. Mol. Cell. Biol. 10:615-624.
  7. Compton, D. A., Yen, T. J., Cleveland, D. W. (1991) Identification of novel centromere/kinetochore associated proteins using monoclonal antibodies generated against human mitotic chromosome scaffolds. J. Cell Biol. 112:1083-1097.
  8. Yen, T. J., Compton, D. A., Wise, D., Zinkowski, R. P., Brinkley, B. R., Earnshaw, W. C., Cleveland, D. W. (1991) CENP-E, a novel human centromere-associated protein required for progression from metaphase to anaphase. E.M.B.O. 10:1245-1254.
  9. Yen, T. J., Li, G., Schaar, B., Szilak, I., Cleveland, D.W. (1992) CENP-E is a putative kinetochore associated motor that accumulates at mitosis. Nature 359:536-540.
  10. Rattner, J. B., Rao, A., Fritzler, M. J., Yen, T. J. (1993) CENP-F is a ca. 400 kDa kinetochore protein that exhibits a cell-cycle dependent localization. Cell Mot. and Cytosk. 26:214-226.
  11. Brown, K.D., Coulson, R.M., Yen, T.J., Cleveland, D.W. (1994) Cyclin-like accumulation and loss of the putative kinetochore motor CENP-E results from coupling continuous synthesis with specific degradation at the end of mitosis. J. Cell. Biol. 126:1303-1312.
  12. Liao, H., Li, G., and Yen, T.J. (1994) Mitotic regulation of the microtubule crosslinking activity of CENP-E kinetochore protein. Science, 265:394-398.
  13. Testa, J.R., Zhou, J.-Y., Bell D.W., Yen, T.J. (1994) Chromosomal localization of the genes encoding the kinetochore proteins CENP-E and CENP-F to human chromosomes 4q24q25 and 1q32q41, respectively by fluorescence in situ hybridization. Genomics 23:691-693.
  14. Lombillo, V.A., Nislow, C., Yen, T.J., Gelfand, V.I., McIntosh, J.R. (1995) Antibodies to the kinesin motor domain and CENP-E inhibit microtubule depolymerization-dependent motion of chromosomes in vitro. J. Cell Biol. 128:107-116.
  15. Thrower, D.A., Jordan, M.A., Schaar, B.T., Yen, T.J., Wilson, L. (1995) Mitotic HeLa cells contain a CENP-E-associated minus end-directed microtubule motor. EMBO J. 14:918-926.
  16. Liao, H., Winkfein, R.J., Mack, G., Rattner, J.B., Yen, T.J. (1995) CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis. J. Cell. Biol. 130:507-518.

Reviews and Books

  1. Cleveland, D.W. and Yen, T.J. (1989) Mutiple determinants of eukaryotic mRNA stability. The New Biologist 1:121-126.
  2. Yen, T.J. (1995) Motor Proteins in Mitosis and Meiosis. In: The Cytoskeleton: Structure and Assembly, Volume 1, pp. 87-122. Eds. J.E. Hesketh and Z.F. Pryme, JAI, publisher.
  3. Yen, T.J. and Schaar, B.T. (1996) Kinetochore function: molecular motors, switches and gates. Current Opinion in Cell Biology, 8:381-388.

 

 
Pennsylvania Muscle Institute
Perelman School of Medicine University of Pennsylvania
Director: E. Michael Ostap, Ph.D.

700A Clinical Research Building Philadelphia, PA 19104-6085 Phone: (215) 573-9758 Fax: (215) 898-2653