240-kDa proteasome inhibitor (CF-2) is identical to delta-aminolevulinic acid dehydratase.
1994; Elsevier BV; Volume: 269; Issue: 17 Linguagem: Inglês
10.1016/s0021-9258(18)99885-6
ISSN1083-351X
AutoresGary Guo, Min Gu, Joseph D. Etlinger,
Tópico(s)Porphyrin Metabolism and Disorders
ResumoThe 240-kDa proteasome inhibitor has been reported to be an ATP-stabilized component (CF-2) of the 26 S proteasome complex.We now report that this inhibitory factor is indistinguishable from 6-aminolevulinic acid dehydratase (ALAD), the second enzyme in the pathway of heme synthesis, based upon the following observations: 1) common sequence of the first 14 N-terminal amino acids; 2) identical migration on native and SDSpolyacrylamide gel electrophoresis; 3) identical isoelectric points of pH 7.1; 4) cross-reactivity of specific polyclonal antibodies; 5 ) similar dehydratase and proteasome inhibitor specific activities in both proteins; and 6) the presence of both activities in recombinant ALAD.The dual role of this protein as CF-2 in the ATP/ ubiquitin-dependent pathway and in heme synthesis may be an example of "gene sharing" and explains the unexpected abundance of ALAD noted in earlier studies.Proteasomes are large (20 S, 700 kDa) multicatalytic protease complexes that are implicated in the degradation of abnormal proteins, transcription factors, oncoproteins, and cyclins as well as i n antigen processing (1-6).Many studies now indicate that the 20 S proteasome serves as a ''barrel''-shaped proteolytic core of a larger 26 S complex, which catalyzes ATP-dependent degradation of proteins that are targeted via the att a c h m e n t of multiple molecules of ubiquitin, an 8-kDa protein (2, 5 , 6).In addition to the 20-32-kDa 20 S proteasome subunits, the 26 S complex contains approximately 12 additional subunits (42-110 kDa), including a putative ATPase (S4), which form a "ball" component (6).Presumably, these components function in substrate recognition and regulation of ATPdependent activity.The 26 S proteasome complex can be assembled in an ATPdependent manner from three factors (CF-1, CF-2, and CF-3) ( 5 , 7).CF-3 is known to be the 20 S proteasome (8, 91, whereas CF-1 is thought to be a multimeric proteasome activator (1) and CF-2 an ATP-stabilized inhibitor of the proteasome (10-12).Presumably CF-1 and CF-2 together are similar or identical to tutes of Health and the Muscular Dystrophy Association.The costs of
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