TY - JOUR
T1 - Tumor suppressor ARF degrades B23, a nucleolar protein involved in ribosome biogenesis and cell proliferation
AU - Itahana, Koji
AU - Bhat, Krishna P.
AU - Jin, Aiwen
AU - Itahana, Yoko
AU - Hawke, David
AU - Kobayashi, Ryuji
AU - Zhang, Yanping
N1 - Funding Information:
We thank Drs. Judith Campisi, Guillermina Lozano, Sandy Chang, Mien-Chie Hung, and Michael Van Dyke for providing materials; Drs. Wei-Ya Xia, Tomoo Iwakuma, and Kevin O'Keefe for technical support. Y. Z. is a recipient of a Career Award in Biomedical Science from the Burroughs Wellcome Fund and a Howard Temin Award from National Cancer Institute. This study was supported by the M.D. Anderson Research Trust Fund and NIH grant (to Y.Z.).
PY - 2003/11
Y1 - 2003/11
N2 - The tumor suppressor ARF induces a p53-dependent and -independent cell cycle arrest. Unlike the nucleoplasmic MDM2 and p53, ARF localizes in the nucleolus. The role of ARF in the nucleolus, the molecular target, and the mechanism of its p53-independent function remains unclear. Here we show that ARF interacts with B23, a multifunctional nucleolar protein involved in ribosome biogenesis, and promotes its polyubiquitination and degradation. Overexpression of B23 induces a cell cycle arrest in normal fibroblasts, whereas in cells lacking p53 it promotes S phase entry. Conversely, knocking down B23 inhibits the processing of preribosomal RNA and induces cell death. Further, oncogenic Ras induces B23 only in ARF null cells, but not in cells that retain wild-type ARF. Together, our results reveal a molecular mechanism of ARF in regulating ribosome biogenesis and cell proliferation via inhibiting B23, and suggest a nucleolar role of ARF in surveillance of oncogenic insults.
AB - The tumor suppressor ARF induces a p53-dependent and -independent cell cycle arrest. Unlike the nucleoplasmic MDM2 and p53, ARF localizes in the nucleolus. The role of ARF in the nucleolus, the molecular target, and the mechanism of its p53-independent function remains unclear. Here we show that ARF interacts with B23, a multifunctional nucleolar protein involved in ribosome biogenesis, and promotes its polyubiquitination and degradation. Overexpression of B23 induces a cell cycle arrest in normal fibroblasts, whereas in cells lacking p53 it promotes S phase entry. Conversely, knocking down B23 inhibits the processing of preribosomal RNA and induces cell death. Further, oncogenic Ras induces B23 only in ARF null cells, but not in cells that retain wild-type ARF. Together, our results reveal a molecular mechanism of ARF in regulating ribosome biogenesis and cell proliferation via inhibiting B23, and suggest a nucleolar role of ARF in surveillance of oncogenic insults.
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U2 - 10.1016/S1097-2765(03)00431-3
DO - 10.1016/S1097-2765(03)00431-3
M3 - Article
C2 - 14636574
AN - SCOPUS:0345276485
SN - 1097-2765
VL - 12
SP - 1151
EP - 1164
JO - Molecular cell
JF - Molecular cell
IS - 5
ER -