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Facilitation of proteasomal degradation of p27 Kip1 by N‐terminal cleavage and their sequence requirements
Author(s) -
Hirano Katsuya,
Ihara Eikichi,
Hirano Mayumi,
Nishimura Junji,
Nawata Hajime,
Kanaide Hideo
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.08.014
Subject(s) - cleavage (geology) , degradation (telecommunications) , cleavage stimulation factor , proteasome , chemistry , proteolysis , cleavage factor , biochemistry , biology , enzyme , telecommunications , paleontology , fracture (geology) , computer science , messenger rna , gene
The sequence requirement for N‐terminal cleavage and the proteasomal degradation of p27 Kip1 and their relationship was investigated. Residues 5–8 were required for the cleavage and the mutation of S10 to E inhibited the cleavage. The C‐terminal PEST sequence was necessary for the degradation and residue R165 was found to play an important role in the degradation. The inhibition of the cleavage by deleting residues 5–8 inhibited the degradation, while the fragment mimicking the cleavage product accelerated the degradation. Both the cleavage and degradation demonstrated a similar sensitivity toward proteasome inhibitors and ATP depletion. These two processes are thus suggested to be tightly linked and sequential.