Arno L. Greenleaf (Primary)
Gene Function and Regulation, Nucleic Acids Biochemistry, RNA Biochemistry
0034 Carl Building, Duke Box 3711,
Durham, NC 27710
My laboratory studies the mechanisms by which different activities in the cell nucleus are connected to the transcription machinery via interactions with the hyper-phosphorylated C-terminal repeat domain (PCTD) of elongating RNA polymerase II. Differential phosphorylation of the CTD, as the RNAP proceeds through successive stages of transcription, orchestrates sequential recruitment of factors to the transcriptase; this serves to coordinate RNA processing events and mRNA nuclear export with gene transcription. To gain a thorough understanding of relevant phosphorylation events on the PCTD, we identified the principal elongation-phase CTD kinase activities in three different eukaryotes, yeast (yCtk1), Drosophila (dCDK12) and humans (hCDK12 & 13). In addition, we described a novel set of phosphoCTD-associating proteins (“PCAPs”) that we now are investigating primarily in human cells. Our results revealed novel roles for elongating RNAPII, and they engendered several totally new lines of investigation.
Recently hCDK12 was shown to be a tumor suppressor for ovarian cancer, and our investigations of this kinase will illuminate its features that, when mutated, can lead to ovarian cancer.
In another cancer-related project, we are identifying drug targets for a new class of drugs to be aimed at ovarian and breast cancers.
- AAAS Fellows. American Association for the Advancement of Science, The. 2012
- Phosphorylation and Functions of the RNA Polymerase CTD awarded by National Institutes of Health2011 - 2016
- Role of PhosphoCTD in Spliceosome Assembly awarded by National Science Foundation 2001 - 2004
- Ctd Kinase And Transcription Dynamics awarded by National Institutes of Health 1996 - 1999
- Ctd Kinase And Rna Polymerase Ii Phosphorylation awarded by National Institutes of Health1988 - 1999
- Transcriptase Kinase From Yeast And Drosophila awarded by National Institutes of Health1988 - 1996
- Rna Polymerase Ii Subunits And Transcription Factors awarded by National Institutes of Health1990 - 1996
- Transcriptase Kinases From Yeast And Drosophila awarded by National Institutes of Health1993 - 1995
- Transcriptase Kinase From Drosophila And Yeast awarded by National Institutes of Health1990 - 1991
- Transcriptase Kinase From Droxophila And Yeast awarded by National Institutes of Health1989 - 1991
- Biochemical Genetics Of Drosophila Rna Polymerase Ii awarded by National Institutes of Health1989 - 1990
- Ph.D., Harvard University 1974
- Bartkowiak, B, and Greenleaf, AL. "Expression, purification, and identification of associated proteins of the full-length hCDK12/CyclinK complex." The Journal of biological chemistry 290, no. 3 (January 2015): 1786-1795. Full Text
- Liu, J, Fan, S, Lee, CJ, Greenleaf, AL, and Zhou, P. "Specific interaction of the transcription elongation regulator TCERG1 with RNA polymerase II requires simultaneous phosphorylation at Ser2, Ser5, and Ser7 within the carboxyl-terminal domain repeat." J Biol Chem 288, no. 15 (April 12, 2013): 10890-10901. Full Text Link to Item
- Winsor, TS, Bartkowiak, B, Bennett, CB, and Greenleaf, AL. "A DNA damage response system associated with the phosphoCTD of elongating RNA polymerase II." PLoS One 8, no. 4 (2013): e60909-. Full Text Link to Item
- Möller, A, Xie, SQ, Hosp, F, Lang, B, Phatnani, HP, James, S, Ramirez, F, Collin, GB, Naggert, JK, Babu, MM, Greenleaf, AL, Selbach, M, and Pombo, A. "Proteomic analysis of mitotic RNA polymerase II reveals novel interactors and association with proteins dysfunctional in disease." Molecular & cellular proteomics : MCP 11, no. 6 (2012): M111.011767-. Full Text
- Möller, A, Xie, SQ, Hosp, F, Lang, B, Phatnani, HP, James, S, Ramirez, F, Collin, GB, Naggert, JK, Babu, MM, Greenleaf, AL, Selbach, M, and Pombo, A. "Proteomic analysis of mitotic RNA polymerase II reveals novel interactors and association with proteins dysfunctional in disease." Molecular and Cellular Proteomics 11, no. 6 (2012). Full Text