Nuclear localization of Tob is important for regulation of its antiproliferative activity.
TOB: is a member of an antiproliferative gene family that includes btg1, pc3/tis21/btg2, pc3b, ana/btg3, and tob2. Exogenous overexpression of the family proteins suppresses cell proliferation. These proteins participate in transcriptional regulation of several genes. Here, we show that Tob is a nuclear protein that is imported into the nucleus through a nuclear localization signal (NLS)-mediated mechanism. Mutation in the NLS sequence of Tob affects its nuclear localization and impairs antiproliferative activity. Additionally, Tob contains a nuclear export signal (NES). In oncogenic ErbB2-transformed cells, nuclear export of Tob is facilitated by NES-mediated mechanism, resulting in decrease of its antiproliferative activity. These results indicate that regulation of nuclear localization of Tob is important for its antiproliferative activity.
Kawamura-Tsuzuku
Junko
J
Division of Oncology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan.
Suzuki
Toru
T
Yoshida
Yutaka
Y
Yamamoto
Tadashi
T
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D002453:Cell Cycle; D002455:Cell Division / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D019913:Nuclear Localization Signals / Q000235:genetics; D013347:Subcellular Fractions / Q000378:metabolism
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019913:Nuclear Localization Signals; C490903:Tob1 protein, mouse