Li X, Coffino P
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Mol Cell Biol. 1993 Apr;13(4):2377-83. doi: 10.1128/mcb.13.4.2377-2383.1993.
Polyamine-mediated degradation of vertebrate ornithine decarboxylase (ODC) is associated with the production of antizyme, a reversible tightly binding protein inhibitor of ODC activity. The interaction of antizyme with a binding element near the N terminus of ODC is essential but not sufficient for regulation of the enzyme by polyamines (X. Li and P. Coffino, Mol. Cell. Biol. 12:3556-2562, 1992). We now show that a second element present at the C terminus is required for the degradation process. Antizyme caused a conformational change in ODC, which made the C terminus of ODC more accessible. Blocking the C terminus with antibody prevented degradation. Tethering the C terminus by creating a circularly permuted, enzymatically active form of ODC prevented antizyme-mediated degradation. These data elucidate a form of feedback regulation whereby excess polyamines induce destruction of ODC, the enzyme that initiates their biosynthesis.
多胺介导的脊椎动物鸟氨酸脱羧酶（ODC）降解与抗酶的产生有关，抗酶是一种可逆的紧密结合蛋白，可抑制ODC活性。抗酶与ODC N端附近的结合元件相互作用对于多胺对该酶的调节至关重要，但并不充分（X. Li和P. Coffino，《分子细胞生物学》12:3556 - 2562，1992）。我们现在表明，降解过程需要ODC C端存在的第二个元件。抗酶导致ODC构象发生变化，使ODC的C端更容易接近。用抗体封闭C端可阻止降解。通过创建一种环状排列的、具有酶活性的ODC形式来束缚C端，可防止抗酶介导的降解。这些数据阐明了一种反馈调节形式，即过量的多胺诱导ODC（启动其生物合成的酶）的破坏。
