Vanderbilt University School of Medicine

Tansey, William P , Ph. D.
Professor of Cell and Developmental Biology

Lab Url: http://www.tanseylab.com

Phone Number: 615-322-1993

Email Address:william.p.tansey@vanderbilt.edu

Tansey, William's picture

Office Address   Mailing Address

Suite 4140 MRB III

Vanderbilt University Medical Center Suite 4140 MRB III 37232-8240


Research Keywords
Oncoproteins, Ubiquitin, Proteolysis,Biochemistry,Cancer,Chromatin,Gene regulation,Genetics,Mouse,Post-transcriptional modification,Transcription,Transcription factor,Yeast

Research Specialty
Oncoproteins, Ubiquitin, Proteolysis

Research Description
Transcription and ubiquitin-mediated proteolysis are two processes that might seem to have little in common. Transcription is the first step in the life of any protein; proteolysis the last. Despite the disparate nature of these processes, a growing body of evidence suggests that components of the ubiquitin-proteasome system are intimately involved in the regulation of gene expression. Research in my laboratory is geared toward understanding how these two processes intersect, and the consequences of this intersection for cellular growth control.

Our current research is divided into two areas. One area is focused on revealing the basic mechanisms that connect the transcription and ubiquitin systems. We have previously found that the destruction of transcription factors is intimately tied to their ability to activate transcription, and that components of the proteasome play an essential role in the regulation of histone modifications. We are currently studying how prototypical transcription factors, such as the yeast activator Gal4, interact with ubiquitin and with the proteasome to regulate gene expression.

Our second area of research is focused on understanding how the destruction of transcription factors impacts mammalian cell growth control. These studies center on Myc, an oncoprotein transcription factor that features prominently in human cancer. We have previously found that Myc is rapidly destroyed by the ubiquitin-system, and that oncogenic mutations within Myc stabilize the protein, allowing it to accumulate. We seek to identify the cellular machinery that targets Myc for ubiquitin-mediated destruction, and learn how the regulation of Myc turnover--and loss of control of this process--relates to human cancer.

Publications
Lee, SB, Kim, JJ, Chung, JS, Lee, MS, Lee, KH, Kim, BS, Tansey, WP, Do Yoo, Y. Romo1 is a negative-feedback regulator of Myc. J Cell Sci, 124(Pt 11), 1911-24, 2011.

Leung, A, Cajigas, I, Jia, P, Ezhkova, E, Brickner, JH, Zhao, Z, Geng, F, Tansey, WP. Histone H2B ubiquitylation and H3 lysine 4 methylation prevent ectopic silencing of euchromatic loci important for the cellular response to heat. Mol Biol Cell, 22(15), 2741-2753, 2011.

Simpson, DR, Yu, M, Zheng, S, Zhao, Z, Muthuswamy, SK, Tansey, WP. Epithelial cell organization suppresses Myc function by attenuating Myc expression. Cancer Res, 71(11), 3822-30, 2011.

Thomas, LR, Tansey, WP. Proteolytic control of the oncoprotein transcription factor Myc. Adv Cancer Res, 110, 77-106, 2011.

Zheng, S, Tansey, WP, Hiebert, SW, Zhao, Z. Integrative network analysis identifies key genes and pathways in the progression of hepatitis C virus induced hepatocellular carcinoma. BMC Med Genomics, 4(1), 62, 2011.

Collins, GA, Gomez, TA, Deshaies, RJ, Tansey, WP. Combined chemical and genetic approach to inhibit proteolysis by the proteasome. Yeast, 27(11), 965-74, 2010.

Wang, X, Muratani, M, Tansey, WP, Ptashne, M. Proteolytic instability and the action of nonclassical transcriptional activators. Curr Biol, 20(9), 868-71, 2010. PMCID:3033761

Chakraborty, AA, Tansey, WP. Adenoviral E1A function through Myc. Cancer Res, 69(1), 6-9, 2009.

Chakraborty, AA, Tansey, WP. Inference of cell cycle-dependent proteolysis by laser scanning cytometry. Exp Cell Res, 315(10), 1772-8, 2009. PMCID:2680938

Collins, GA, Lipford, JR, Deshaies, RJ, Tansey, WP. Gal4 turnover and transcription activation. Nature, 461(7265), E7; discussion E8, 2009. PMCID:3072683

Daulny, A, Tansey, WP. Damage control: DNA repair, transcription, and the ubiquitin-proteasome system. DNA Repair (Amst), 8(4), 444-8, 2009.

Daulny, A, Geng, F, Muratani, M, Geisinger, JM, Salghetti, SE, Tansey, WP. Modulation of RNA polymerase II subunit composition by ubiquitylation. Proc Natl Acad Sci U S A, 105(50), 19649-54, 2008. PMCID:2604917

Geng, F, Tansey, WP. Polyubiquitylation of histone H2B. Mol Biol Cell, 19(9), 3616-24, 2008. PMCID:2526708

Kurland, JF, Tansey, WP. Myc-mediated transcriptional repression by recruitment of histone deacetylase. Cancer Res, 68(10), 3624-9, 2008.

Leung, A, Geng, F, Daulny, A, Collins, G, Guzzardo, P, Tansey, WP. Transcriptional control and the ubiquitin-proteasome system. Ernst Schering Found Symp Proc, (1), 75-97, 2008.

Tworkowski, KA, Chakraborty, AA, Samuelson, AV, Seger, YR, Narita, M, Hannon, GJ, Lowe, SW, Tansey, WP. Adenovirus E1A targets p400 to induce the cellular oncoprotein Myc. Proc Natl Acad Sci U S A, 105(16), 6103-8, 2008. PMCID:2329713

Tansey, WP. Pulse-chase assay for measuring protein stability in yeast. CSH Protoc, 2007, pdb.prot4641, 2007. PMCID:2329713

Tansey, WP. Yeast Chromatin Immunoprecipitation (ChIP) Assay. CSH Protoc, 2007, pdb.prot4642, 2007. PMCID:2329713

Tansey, WP. Denaturing protein immunoprecipitation from yeast. CSH Protoc, 2007, pdb.prot4643, 2007. PMCID:2329713

Tansey, WP. Nondenaturing protein immunoprecipitation from Mammalian cells. CSH Protoc, 2007, pdb.prot4620, 2007. PMCID:2329713

Collins, GA, Tansey, WP. The proteasome: a utility tool for transcription. Curr Opin Genet Dev, 16(2), 197-202, 2006.

Ezhkova, E, Tansey, WP. Chromatin immunoprecipitation to study protein-DNA interactions in budding yeast. Methods Mol Biol, 313, 225-44, 2006.

Hemann, MT, Bric, A, Teruya-Feldstein, J, Herbst, A, Nilsson, JA, Cordon-Cardo, C, Cleveland, JL, Tansey, WP, Lowe, SW. Evasion of the p53 tumour surveillance network by tumour-derived MYC mutants. Nature, 436(7052), 807-11, 2005.

Herbst, A, Hemann, MT, Tworkowski, KA, Salghetti, SE, Lowe, SW, Tansey, WP. A conserved element in Myc that negatively regulates its proapoptotic activity. EMBO Rep, 6(2), 177-83, 2005. PMCID:1299243

Lee, D, Ezhkova, E, Li, B, Pattenden, SG, Tansey, WP, Workman, JL. The proteasome regulatory particle alters the SAGA coactivator to enhance its interactions with transcriptional activators. Cell, 123(3), 423-36, 2005.

Muratani, M, Kung, C, Shokat, KM, Tansey, WP. The F box protein Dsg1/Mdm30 is a transcriptional coactivator that stimulates Gal4 turnover and cotranscriptional mRNA processing. Cell, 120(6), 887-99, 2005.

Ezhkova, E, Tansey, WP. Proteasomal ATPases link ubiquitylation of histone H2B to methylation of histone H3. Mol Cell, 13(3), 435-42, 2004.

Herbst, A, Salghetti, SE, Kim, SY, Tansey, WP. Multiple cell-type-specific elements regulate Myc protein stability. Oncogene, 23(21), 3863-71, 2004.

Kim, SY, Herbst, A, Tworkowski, KA, Salghetti, SE, Tansey, WP. Skp2 regulates Myc protein stability and activity. Mol Cell, 11(5), 1177-88, 2003.

Muratani, M, Tansey, WP. How the ubiquitin-proteasome system controls transcription. Nat Rev Mol Cell Biol, 4(3), 192-201, 2003.

Tworkowski, KA, Salghetti, SE, Tansey, WP. Stable and unstable pools of Myc protein exist in human cells. Oncogene, 21(55), 8515-20, 2002.

Salghetti, SE, Caudy, AA, Chenoweth, JG, Tansey, WP. Regulation of transcriptional activation domain function by ubiquitin. Science, 293(5535), 1651-3, 2001.

Salghetti, SE, Muratani, M, Wijnen, H, Futcher, B, Tansey, WP. Functional overlap of sequences that activate transcription and signal ubiquitin-mediated proteolysis. Proc Natl Acad Sci U S A, 97(7), 3118-23, 2000. PMCID:16202

Salghetti, SE, Kim, SY, Tansey, WP. Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize Myc. EMBO J, 18(3), 717-26, 1999. PMCID:1171164


Postdoctoral Position Available
Yes

Postdoctoral Position Details
Postdoctoral fellows wanted for an exciting set of new projects on Myc, chromatin, the epigenome, MDS, and melanoma. Please send CV and cover letter to william.p.tansey@vanderbilt.edu. Check us out on the web at www.tanseylab.com.

Updated Date
09/18/2013



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