Abstract

Mammalian ornithine decarboxylase (ODC) is subject to a form of feedback regulation whereby polyamines, the product of the metabolic pathway initiated by ODC, cause a prompt reduction of enzymatic activity when their level becomes high within cells. This process occurs post- translationally, but its mechanism is not well understood. ODC of the parasite Trypanosome brucei is structurally similar to mammalian ODC, but is not regulated in this way. Utilizing cloned genes from the parasite and from mouse, we will employ reverse-genetic and biochemical approaches to studying this problem. In addition, transgenic mice will be used to determine whether the regulatory process mediates significant biological functions in the intact organism.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM045335-04
Application #
2183089
Study Section
Medical Biochemistry Study Section (MEDB)
Project Start
1991-01-01
Project End
1994-12-31
Budget Start
1994-01-01
Budget End
1994-12-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Erales, Jenny; Coffino, Philip (2014) Ubiquitin-independent proteasomal degradation. Biochim Biophys Acta 1843:216-21
Too, Priscilla Hiu-Mei; Erales, Jenny; Simen, Joana Danica et al. (2013) Slippery substrates impair function of a bacterial protease ATPase by unbalancing translocation versus exit. J Biol Chem 288:13243-57
Park, Soyeon; Li, Xueming; Kim, Ho Min et al. (2013) Reconfiguration of the proteasome during chaperone-mediated assembly. Nature 497:512-6
Erales, Jenny; Hoyt, Martin A; Troll, Fabian et al. (2012) Functional asymmetries of proteasome translocase pore. J Biol Chem 287:18535-43
Henderson, Allen; Erales, Jenny; Hoyt, Martin A et al. (2011) Dependence of proteasome processing rate on substrate unfolding. J Biol Chem 286:17495-502
Hoyt, Martin A; Zhang, Mingsheng; Coffino, Philip (2005) Probing the ubiquitin/proteasome system with ornithine decarboxylase, a ubiquitin-independent substrate. Methods Enzymol 398:399-413
Verma, Rati; Peters, Noel R; D'Onofrio, Mariapina et al. (2004) Ubistatins inhibit proteasome-dependent degradation by binding the ubiquitin chain. Science 306:117-20
Zhang, Mingsheng; MacDonald, Alasdair I; Hoyt, Martin A et al. (2004) Proteasomes begin ornithine decarboxylase digestion at the C terminus. J Biol Chem 279:20959-65
Zhang, Mingsheng; Coffino, Philip (2004) Repeat sequence of Epstein-Barr virus-encoded nuclear antigen 1 protein interrupts proteasome substrate processing. J Biol Chem 279:8635-41
Zhang, Mingsheng; Pickart, Cecile M; Coffino, Philip (2003) Determinants of proteasome recognition of ornithine decarboxylase, a ubiquitin-independent substrate. EMBO J 22:1488-96

Showing the most recent 10 out of 23 publications