We are characterizing a novel interaction between Rev, a regulatory HIV protein, and microtubules. Data to date suggest that Rev interacts with microtubules by a mechanism shared with certain anti-cancer drugs and proteins of the Kinesin-13 family that are potent regulators of the mitotic spindle. Taken together, this raises the possibility that Rev:microtubule interactions may contribute to cytoskeletal pathologies observed in HIV-infected cells and suggests that Rev may represent a novel source of antiproliferative peptides. We are comparing and contrasting the inhibitory effects on wild-type and mutant Rev proteins on microtubule function in vitro and in vivo.
My lab also has a history of studying the biological function of single residues of O-linked N-acetyl-D-glucosamine (O-GlcNAc) that modify many nuclear and cytosolic proteins essential for signal transduction, cytoskeletal architecture, transcription, and nuclear transport. O-GlcNAc addition is dynamic and the extent of glycosylation can change rapidly in response to different stimuli. The functions and subcellular distributions of O-GlcNAc-modified proteins suggest that this type of glycosylation coordinates many diverse cellular responses. The finding that unusual patterns of glycosylation are associated with certain human diseases including Alzheimer’s disease, diabetes, and certain cancers is consistent with this hypothesis. Our research uses recombinant DNA technology and traditional biochemical techniques to examine the effects of altered glycosylation upon microtubule function in vitro and in vivo.
Stephanie C. Ems-McClung, Kathleen M. Hertzer, Xin Zhang, Mill W. Miller, and Claire E. Walczak. 2007. The Interplay of the N- and C-Terminal Domains of MCAK Control Microtubule Depolymerization Activity and Spindle Assembly. MBC 18(1)282-294
Jeff Horn, Isabel Lopez, Mill Miller, Julian Gomez-Cambronero. 2005. The uncovering of a novel regulatory mechanism for PLD2: Formation of a ternary complex with protein tyrosine phosphatase PTP1B and growth factor receptor-bound protein GRB2. BBRC 332:58-67.
Fang, B and M. W. Miller. 2001. Use of galactosyltransferase to assess the biological function of O-linked N-acetyl-D-glucosamine: a potential role for O-GlcNAc in the cell cycle. Exp. Cell Res. 263:243-253.
Watts, N., D. L. Sackett, R. D. Ward, M. W. Miller, P. T. Wingfield, S. S. Stahl, and A. Steven, and D. Sackett. 2000. Interaction of HIV-1 Rev with Microtubules. J. Cell Biol. 150(2):349-60.