Harvard University - Department of Molecular & Cellular Biology

RAYMOND L. ERIKSON

Erikson
John F. Drum American Cancer Society Professor of Cellular and Developmental Biology

Email: erikson@mcb.harvard.edu
Phone: 617-495-5386

Mail: BL 4070C
The Biological Labs
16 Divinity Ave
Cambridge, MA  02138

Members of the Erikson Lab
List of Publications from PubMed

Courses

MCB 326. Biochemical Virology
Catalog Number: 243  View Course Website
Term: Fall Term; Repeated Spring Term 2013-2014.   Credit: Half course.
Instructor: Raymond Erikson
Course Level: Graduate Course
BIOPHYS 348. Protein Kinases, Reversible Protein Phosphorylation
Catalog Number: 4964  View Course Website
Term: Fall Term; Repeated Spring Term 2013-2014.   Credit: Half course.
Instructor: Raymond Erikson
Course Level: Graduate Course
VIROLOGY 332. Protein Phosphorylation and Gene Expression in Normal and Transformed Cells
Catalog Number: 9093  View Course Website
Term: Fall Term; Repeated Spring Term 2013-2014.   Credit: Half course.
Instructor: Raymond Erikson
Course Level: Graduate Course
(View all MCB Courses)

Research

Reversible protein phosphorylation and cell proliferation.

Our studies focus on the role of reversible phosphorylation in the regulation of essential steps in cell proliferation. Recently we have focused on the functions and regulation of polo-like kinases (Plk) in mammalian cells. Three mammalian Plks have been identified; Plk1 is expressed during M phase and cytokinesis, whereas Plk2 (Snk) and Plk3 (Fnk) are expressed in other phases of the cell cycle. These enzymes are characterized by their similar N-terminal catalytic domains, as well as a C-terminal domain with highly conserved sequences termed the polo box. We have previously demonstrated that the polo box directs Plk1 to specific cellular locations and is required together with protein kinase activity to promote cell proliferation. Plk1 localizes to centrosomes and the spindle poles at metaphase, in the central spindle during anaphase, and at the midbody during cytokinesis. Plk1 has been implicated in centrosome maturation, bipolar spindle formation and activation of the anaphase-promoting complex.

We have determined that intramolecular interactions of the catalytic and non-catalytic domains, as well as phosphorylation of Plk1 regulate the activation of its protein kinase activity. Our use of small interfering RNA to deplete Plk1 in cells demonstrates that it is required for centrosome duplication, anaphase and cytokinesis in mammalian cells. Cancer cells depleted of Plk1 rapidly undergo apoptosis. We are investigating whether this occurs in a wide variety of tumor cells or normal cells, as Plk1 may be a useful chemotherapy target.

A major effort in our laboratory is directed at identification and characterization of Plk1 substrates. Mitotic motor proteins, including the mitotic kinesin-like protein (MKLP1/CHO1), are of special interest. We also study the changes in function of substrates after mutation of sites phosphorylated by Plk1.

Publications

Sütterlin, C., Lin, C. Y., Feng, Y., Ferris, D. K., Erikson, R. L., and Malhotra, V. (2001). Polo-like kinase is required for the fragmentation of pericentriolar Golgi stacks during mitosis. Proc Natl Acad Sci USA , 98, 9128-32.

Jang, Y. J., Lin, C. Y., Ma, S., and Erikson, R. L. (2002). Functional studies on the role of the C-terminal domain of mammalian polo-like kinase. Proc Natl Acad Sci USA 99, 1984-89.

Liu, X. and Erikson, R. L. (2002). Activation of Cdc2/cyclin B and inhibition of centrosome amplification in cells depleted of Plk1 by siRNA. Proc Natl Acad Sci USA 99, 8672-76.

Jang, Y. J., Ma, S., Terada, Y., and Erikson, R. L. (2002). Phosphorylation of Threonine-210 and the role of Serine-137 in the regulation of mammalian polo-like kinase. J Biol Chem 277, 44115-20.

Ma, S., Liu, M. A., Yuan, Y. L., and Erikson, R. L. (2003). The serum-inducible protein kinase Snk is a G(1) phase polo-like kinase that is inhibited by the calcium- and integrin-binding protein CIB. Mol Cancer Res 1, 376-84.

Liu, X. and Erikson, R. L. (2003) Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells. Proc Natl Acad Sci USA 100, 5789-5794.

Bélanger, L-F., Roy, S., Tremblay, M., Brott, B., Steff, A-M., Mourad, W., Hugo, P., Erikson, R. L., and Charron, J. (2003). MEK2 is dispensable for mouse growth and development. Mol Cell Biol 23, 4778-4787.

Zhou, T., Aumais, J., Liu, X., Yu-Lee, L. Y., and Erikson, R. L. (2003) A role for Plk1 phosphorylation of NudC in cytokinesis. Developmental Cell 5, 127-138.

Ma, S., Charron, J., and Erikson, R. L. (2003). The role of Plk2 (Snk) in mouse development and cell proliferation. Mol Cell Biol 23, 6936-43.

Liu, X., and Erikson, R. L. (2003) Polo-like kinase 1 in the life and death of cancer cells. Cell Cycle 2, 424-425.

Liu, X., Yan, S., Zhou, T., Terada, Y., and Erikson, R. L. (2004) The MAP kinase pathway is required for entry into mitosis and cell survival. Oncogene 23, 763-76.

Liu, X., Zhou, T., Kuriyama, R., and Erikson, R. L. (2004) Molecular interactions of Polo-like kinase 1 with mitotic kinesin-like protein CHO1/MKLP-1. J Cell Sci 117, 3233-46.

Liu, X., Lin, C.-Y., Lei, M., Yan, S., Zhou, T., and Erikson, R. L. (2005)  CCT chaperonin complex is required for the biogenesis of functional Plk1.  Mol Cell Biol 25, 4993-5010.

Liu, X., Lei, M., and Erikson, R. L. (2006)  Normal cells, but not cancer cells, survive severe Plk1 depletion.  Mol Cell Biol 26, 2093-2108.

Zimmerman, W. C. and Erikson, R. L. (2007) Polo-like kinase 3 is required for entry into S phase. Proc Natl Acad Sci USA 104, 1847-52.

Liu, X., and Erikson, R. L. (2007) The nuclear localization signal of mitotic kinesin-like protein Mklp-1: effect on Mklp-1 function during cytokinesis. Biochem Biophys Res Commun. 353, 960-4.

Zimmerman, W.C., and Erikson, R. L. (2007) Finding Plk3. Cell Cycle 6, 1314-8.

Lee, K.S., Park, J.-E., Young, H.K., Soung, N.-K., and Erikson, R. L. (2008) Mechanisms of mammalian polo-like kinase 1 (Plk1) localization: Self- versus non-self-priming model. Cell Cycle 7(2), 141-5.

Lei, M., and Erikson, R. L. (2008) Plk1 depletion in non-transformed diploid cells activates the DNA-damage checkpoint. Oncogene 27(28), 3935-43.

Yim, H., and Erikson, R. L. (2009) Polo-like kinase-1 depletion induces DNA damage in early S prior to caspase activation. Mol Cell Biol 29, 2609-21.

updated: 04/15/2014