Ubiquitin-aldehyde: a general inhibitor of ubiquitin-recycling processes

Journal Article · Wed Apr 01 00:00:00 EST 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.7.1829· OSTI ID:6072585

Hershko, A; Rose, I A

The generation and characterization of ubiquitin (Ub)-aldehyde, a potent inhibitor of Ub-C-terminal hydrolase, has previously been reported. The authors examine the action of this compound on the Ub-mediated proteolytic pathway using the system derived from rabbit reticulocytes. Addition of Ub-aldehyde was found to strongly inhibit breakdown of added /sup 125/I-labeled lysozyme, but inhibition was overcome by increasing concentrations of Ub. The following evidence shows the effect of Ub-aldehyde on protein breakdown to be indirectly caused by its interference with the recycling of Ub, leading to exhaustion of the supply of free Ub: (i) Ub-aldehyde markedly increased the accumulation of Ub-protein conjugates coincident with a much decreased rate of conjugate breakdown; (ii) release of Ub from isolated Ub-protein conjugates in the absence of ATP (and therefore not coupled to protein degradation) is markedly inhibited by Ub-aldehyde. On the other hand, the ATP-dependent degradation of the protein moiety of Ub conjugates, which is an integral part of the proteolytic process, is not inhibited by this agent; (iii) direct measurement of levels of free Ub showed a rapid disappearance caused by the inhibitor. The Ub is found to be distributed in derivatives of a wide range of molecular weight classes. It thus seems that Ub-aldehyde, previously demonstrated to inhibit the hydrolysis of Ub conjugates of small molecules, also inhibits the activity of a series of enzymes that regenerate free Ub from adducts with proteins and intermediates in protein breakdown.

• Research Organization: Institute for Cancer Research, Philadelphia, PA
• OSTI ID: 6072585
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:7
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
BIOCHEMISTRY
LYSOZYME
RETICULOCYTES
BIOLOGICAL PATHWAYS
ATP
ELECTROPHORESIS
ENZYME INHIBITORS
IODINE 125
POLYPEPTIDES
PROTEOLYSIS
RABBITS
TRITIUM COMPOUNDS
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHEMICAL REACTIONS
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
ERYTHROCYTES
GLYCOSYL HYDROLASES
HYDROLASES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
MATERIALS
NUCLEI
NUCLEOTIDES
O-GLYCOSYL HYDROLASES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDES
PROTEINS
RADIOISOTOPES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques