RRC ID 45119
著者 Maehama T, Kawahara K, Nishio M, Suzuki A, Hanada K.
タイトル Nucleolar stress induces ubiquitination-independent proteasomal degradation of PICT1 protein.
ジャーナル J Biol Chem
Abstract The nucleolar protein PICT1 regulates tumor suppressor p53 by tethering ribosomal protein L11 within the nucleolus to repress the binding of L11 to the E3 ligase MDM2. PICT1 depletion results in the release of L11 to the nucleoplasm to inhibit MDM2, leading to p53 activation. Here, we demonstrate that nucleolar stress induces proteasome-mediated degradation of PICT1 in a ubiquitin-independent manner. Treatment of H1299 cells with nucleolar stress inducers, such as actinomycin D, 5-fluorouridine, or doxorubicin, induced the degradation of PICT1 protein. The proteasome inhibitors MG132, lactacystin, and epoxomicin blocked PICT1 degradation, whereas the inhibition of E1 ubiquitin-activating enzyme by a specific inhibitor and genetic inactivation fail to repress PICT1 degradation. In addition, the 20 S proteasome was able to degrade purified PICT1 protein in vitro. We also found a PICT1 mutant showing nucleoplasmic localization did not undergo nucleolar stress-induced degradation, although the same mutant underwent in vitro degradation by the 20 S proteasome, suggesting that nucleolar localization is indispensable for the stress-induced PICT1 degradation. These results suggest that PICT1 employs atypical proteasome-mediated degradation machinery to sense nucleolar stress within the nucleolus.
巻・号 289(30)
ページ 20802-12
公開日 2014-7-25
DOI 10.1074/jbc.M114.571893
PII S0021-9258(20)47598-2
PMID 24923447
PMC PMC4110288
MeSH Antineoplastic Agents / pharmacology Cell Nucleolus / metabolism* HEK293 Cells HeLa Cells Humans Proteasome Endopeptidase Complex / metabolism* Proteasome Inhibitors / pharmacology Proteolysis* Stress, Physiological / drug effects Stress, Physiological / physiology* Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism* Ubiquitination / drug effects Ubiquitination / physiology*
IF 4.238
引用数 8
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 FM3A tscl.T85 Tsai(RCB0033)