Research in Harlow laboratory focuses on two major topics in the control of mammalian cell proliferation. One portion of the laboratory studies the control of cell cycle progression, and the other is investigating the consequences of losing one of the key negative regulatory proteins, the retinoblastoma tumor suppressor gene product.
A cell's decision to divide rests on its interpretation of a complicated set of positive and negative signals. These signals ultimately control progression through key transition points in the cell cycle, and these transition points are regulated by activation of kinase complexes composed of a catalytic and a regulatory subunit. Recent work from several laboratories has identified multiple catalytic and regulatory subunits, known as cyclin-dependent kinases (cdkÕs) and cyclins respectively, and we are trying to determine what rules govern kinase complex formation, how kinase activities are regulated, and what roles these kinases play in controlling cell cycle progression.
Our work on tumor suppressor gene function has centered on the retinoblastoma gene product (pRB). Loss of this gene is found is seen in many human tumors. The pRB signaling pathway helps control the timing of transcription of key proliferation genes. We are studying how this pathway is regulated and the genes that are downstream targets of this key transcriptional control.
Selected Publications:
Yamasaki, L., T. Jacks, R. Bronson, E. Goillot, E. Harlow, and N. Dyson (1996). Tumor induction and tissue atrophy in mice lacking E2F-1. Cell 85:537-548.
Vidal, M., P. Braun, E. Chen, J. Boeke, and E. Harlow (1996). Genetic characterization of a mammalian protein-protein interaction domain using a two-step genetic selection. Proc. Natl. Acad. Sci. USA. 93:10321-10326.
LaBaer, J., M. Garrett, L. Stevenson, J. Slingerland, C. Sandhu, H. Chou, A. Fattaey, and E. Harlow (1997). New functional activities for the p21 family of CDK inhibitors. Genes and Development, in press.