Specific cleavage of the 70-kDa protein component of the U1 small nuclear ribonucleoprotein is a characteristic biochemical feature of apoptotic cell death.
The U1 small nuclear ribonucleoprotein particle is essential for splicing of precursor mRNA, an activity that depends upon both the RNA and protein components of the U1 particle. One of the U1-specific proteins that is functionally important in this splicing reaction is the 70-kDa protein (U1-70kDa). We report here that U1-70kDa is specifically cleaved in apoptotic cells, resulting in the generation of a 40-kDa fragment. The kinetics of this cleavage coincided with the appearance of cells with apoptotic morphology in the population, and the proportion of 40-kDa fragment observed was markedly increased in apoptotic cells that had become detached from the substratum. Although the inhibitor characteristics of the activity cleaving U1-70kDa suggest that interleukin 1 beta-converting enzyme (ICE) might be responsible, the specific ICE inhibitor N-(N-acetyl-tyrosinyl-valinyl-alaninyl)-3-amino-4-oxob utanoic acid (YVAD-CHO) did not prevent cleavage, and U1-70kDa was not cleaved by purified ICE in vitro. Further study of this novel cleavage and the enzyme responsible will yield information about proteolytic events that might be central in the mechanism and control of apoptosis.
Casciola-Rosen
L A
LA
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Miller
D K
DK
Anhalt
G J
GJ
Rosen
A
A
D017209:Apoptosis; D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry / Q000378:metabolism*; D015843:Serpins / Q000494:pharmacology; D014764:Viral Proteins
D017411:Ribonucleoproteins, Small Nuclear; D015843:Serpins; D014764:Viral Proteins; C074641:interleukin-1beta-converting enzyme inhibitor; D003546:Cysteine Endopeptidases; D020170:Caspase 1