Abstract

Sulfate conjugation (sulfonation) is an important pathway in the biotransformation of steroid hormones. These reactions are catalyzed by a superfamily of cytosolic sulfotransferase (SULT) enzymes. In humans, the SULT2B1 gene encodes two isoforms, SULT2B1a and SULT2B1b, that catalyze the sulfonation of steroid hormones including dehydroepiepiandrosterone and dihydrotestosterone. SULT2B1 is expressed in steroid hormone-responsive tissues including prostate and breast. The goal of this research proposal seeks to elucidate a novel regulatory pathway, catalyzed by SULT2B1, that abrogates steroid- hormone dependent cellular processes. The proposed studies will evaluate the proliferative and transcriptional responses of cells expressing SULT2B1 and naturally occurring polymorphic SULT2B1 alloenzymes toward androgens. In complementary work, the functional significance of an evolutionarily acquired, novel proline-rich domain in SULT2B1 will be evaluated for its contribution to protein-protein interactions. Finally, the functional significance of common genetic SULT2B1 polymorphisms will be evaluated. Together these studies have the potential to elucidate a novel regulatory pathway, catalyzed by SULT2B1, that abrogates steroid hormone-dependent cellular processes in humans.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM065794-01
Application #
6486488
Study Section
Special Emphasis Panel (ZRG1-F06 (20))
Program Officer
Ikeda, Richard A
Project Start
2002-03-11
Project End
2002-11-08
Budget Start
2002-03-11
Budget End
2002-11-08
Support Year
1
Fiscal Year
2002
Total Cost
$31,231
Indirect Cost

  Institution

Name
Institute for Cancer Research
Department
Type
DUNS #
872612445
City
Philadelphia
State
PA
Country
United States
Zip Code
19111

  Publications

Früh, Klaus; Picker, Louis (2017) CD8+ T cell programming by cytomegalovirus vectors: applications in prophylactic and therapeutic vaccination. Curr Opin Immunol 47:52-56
Hansen, Scott G; Wu, Helen L; Burwitz, Benjamin J et al. (2016) Broadly targeted CD8? T cell responses restricted by major histocompatibility complex E. Science 351:714-20
DeVore, M S; Stich, D G; Keller, A M et al. (2015) Note: Time-gated 3D single quantum dot tracking with simultaneous spinning disk imaging. Rev Sci Instrum 86:126102
López, Cesar A; Sethi, Anurag; Goldstein, Byron et al. (2015) Membrane-mediated regulation of the intrinsically disordered CD3? cytoplasmic tail of the TCR. Biophys J 108:2481-2491
Cleyrat, Cédric; Darehshouri, Anza; Steinkamp, Mara P et al. (2014) Mpl traffics to the cell surface through conventional and unconventional routes. Traffic 15:961-82
Cleyrat, Cédric; Darehshouri, Anza; Anderson, Karen L et al. (2013) The architectural relationship of components controlling mast cell endocytosis. J Cell Sci 126:4913-25
Matlawska-Wasowska, K; Ward, E; Stevens, S et al. (2013) Macrophage and NK-mediated killing of precursor-B acute lymphoblastic leukemia cells targeted with a-fucosylated anti-CD19 humanized antibodies. Leukemia 27:1263-74
Steinkamp, Mara P; Winner, Kimberly Kanigel; Davies, Suzy et al. (2013) Ovarian tumor attachment, invasion, and vascularization reflect unique microenvironments in the peritoneum: insights from xenograft and mathematical models. Front Oncol 3:97
Pullen, Nicholas A; Barnstein, Brian O; Falanga, Yves T et al. (2012) Novel mechanism for Fc{epsilon}RI-mediated signal transducer and activator of transcription 5 (STAT5) tyrosine phosphorylation and the selective influence of STAT5B over mast cell cytokine production. J Biol Chem 287:2045-54
Wells, Nathan P; Lessard, Guillaume A; Goodwin, Peter M et al. (2010) Time-resolved three-dimensional molecular tracking in live cells. Nano Lett 10:4732-7

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