NVL2 is a nucleolar AAA-ATPase that interacts with ribosomal protein L5 through its nucleolar localization sequence.
NVL (nuclear VCP-like protein), a member of the AAA-ATPase family, is known to exist in two forms with N-terminal extensions of different lengths in mammalian cells. Here, we show that they are localized differently in the nucleus; NVL2, the major species, is mainly present in the nucleolus, whereas NVL1 is nucleoplasmic. Mutational analysis demonstrated the presence of two nuclear localization signals in NVL2, one of which is shared with NVL1. In addition, a nucleolar localization signal was found to exist in the N-terminal extra region of NVL2. The nucleolar localization signal is critical for interaction with ribosomal protein L5, which was identified as a specific interaction partner of NVL2 on yeast two-hybrid screening. The interaction of NVL2 with L5 is ATP-dependent and likely contributes to the nucleolar translocation of NVL2. The physiological implication of this interaction was suggested by the finding that a dominant negative NVL2 mutant inhibits ribosome biosynthesis, which is known to take place in the nucleolus.
School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan.
Masami
M
Nagahama
Yoshimitsu
Y
Hara
Akihiro
A
Seki
Takeshi
T
Yamazoe
Yumiko
Y
Kawate
Takashi
T
Shinohara
Kiyotaka
K
Hatsuzawa
Katsuko
K
Tani
Mitsuo
M
Tagaya
D000074183:ATPases Associated with Diverse Cellular Activities; D021581:Active Transport, Cell Nucleus; D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002466:Cell Nucleolus / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D019913:Nuclear Localization Signals / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism
D019913:Nuclear Localization Signals; D020033:Protein Isoforms; D021122:Protein Subunits; D012269:Ribosomal Proteins; C029742:ribosomal protein L5; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C500249:NVL protein, human; D008239:Lysine