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Mol. Cells 2009; 27(3): 359-363

Published online March 31, 2009

https://doi.org/10.1007/s10059-009-0046-7

© The Korean Society for Molecular and Cellular Biology

Nuclear Localization of Chfr Is Crucial for Its Checkpoint Function

Young Eun Kwon, Ye Seul Kim, Young Mi Oh, and Jae Hong Seol

Received: December 2, 2008; Accepted: December 5, 2008

Abstract

Chfr, a checkpoint with FHA and RING finger domains, plays an important role in cell cycle progression and tu-mor suppression. Chfr possesses the E3 ubiquitin ligase activity and stimulates the formation of polyubiquitin chains by Ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins, including Plk1 and Aurora A. While Chfr is a nuclear protein that functions within the cell nucleus, how Chfr is localized in the nucleus has not been clearly demonstrated. Here, we show that nuclear localization of Chfr is mediated by nuclear localization signal (NLS) sequences. To reveal the signal sequences responsible for nuclear localization, a short lysine-rich stretch (KKK) at amino acid residues 257-259 was replaced with alanine, which completely abolished nuclear localization. Moreover, we show that nuclear localization of Chfr is essential for its checkpoint function but not for its stability. Thus, our results suggest that NLS-mediated nuclear localization of Chfr leads to its accumulation within the nucleus, which may be important in the regulation of Chfr activation and Chfr-mediated cellular processes, including cell cycle progression and tumor suppression.

Keywords Chfr, nuclear localization signal (NLS) sequence, ubiquitination, Ub-ligase

Article

Research Article

Mol. Cells 2009; 27(3): 359-363

Published online March 31, 2009 https://doi.org/10.1007/s10059-009-0046-7

Copyright © The Korean Society for Molecular and Cellular Biology.

Nuclear Localization of Chfr Is Crucial for Its Checkpoint Function

Young Eun Kwon, Ye Seul Kim, Young Mi Oh, and Jae Hong Seol

Received: December 2, 2008; Accepted: December 5, 2008

Abstract

Chfr, a checkpoint with FHA and RING finger domains, plays an important role in cell cycle progression and tu-mor suppression. Chfr possesses the E3 ubiquitin ligase activity and stimulates the formation of polyubiquitin chains by Ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins, including Plk1 and Aurora A. While Chfr is a nuclear protein that functions within the cell nucleus, how Chfr is localized in the nucleus has not been clearly demonstrated. Here, we show that nuclear localization of Chfr is mediated by nuclear localization signal (NLS) sequences. To reveal the signal sequences responsible for nuclear localization, a short lysine-rich stretch (KKK) at amino acid residues 257-259 was replaced with alanine, which completely abolished nuclear localization. Moreover, we show that nuclear localization of Chfr is essential for its checkpoint function but not for its stability. Thus, our results suggest that NLS-mediated nuclear localization of Chfr leads to its accumulation within the nucleus, which may be important in the regulation of Chfr activation and Chfr-mediated cellular processes, including cell cycle progression and tumor suppression.

Keywords: Chfr, nuclear localization signal (NLS) sequence, ubiquitination, Ub-ligase

Mol. Cells
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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