Dataset Information

Circadian phase-specific degradation of the F-box protein ZTL is mediated by the proteasome.

ABSTRACT: Critical to the maintenance of circadian rhythmicity is the cyclic expression of at least some components of the central oscillator. High-amplitude cycling of mRNA and protein abundance, protein phosphorylation and nuclear/cytoplasmic shuttling have all been implicated in the maintenance of circadian period. Here we use a newly characterized Arabidopsis suspension cell culture to establish that the rhythmic changes in the levels of the clock-associated F-box protein, ZTL, are posttranscriptionally controlled through different circadian phase-specific degradation rates. This proteolysis is proteasome dependent, implicating ZTL itself as substrate for ubiquitination. This demonstration of circadian phase-regulated degradation of an F-box protein, which itself controls circadian period, suggests a novel regulatory feedback mechanism among known circadian systems.

SUBMITTER: Kim WY

PROVIDER: S-EPMC404699 | biostudies-literature | 2003 Apr

REPOSITORIES: biostudies-literature

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Circadian phase-specific degradation of the F-box protein ZTL is mediated by the proteasome.

Kim Woe-Yeon WY Geng Ruishuang R Somers David E DE

Proceedings of the National Academy of Sciences of the United States of America 20030328 8

Critical to the maintenance of circadian rhythmicity is the cyclic expression of at least some components of the central oscillator. High-amplitude cycling of mRNA and protein abundance, protein phosphorylation and nuclear/cytoplasmic shuttling have all been implicated in the maintenance of circadian period. Here we use a newly characterized Arabidopsis suspension cell culture to establish that the rhythmic changes in the levels of the clock-associated F-box protein, ZTL, are posttranscriptional ...[more]

PMID: 12665620

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Project description:The key pathogenic steps leading to spinal muscular atrophy (SMA), a genetic disease characterized by selective motor neuron degeneration, are not fully clarified. The full-length SMN protein (FL-SMN), the main protein product of the disease gene SMN1, plays an established role in the cytoplasm in snRNP biogenesis ultimately leading to mRNA splicing within the nucleus. It is also involved in the mRNA axonal transport. However, to what extent the impairment of these two SMN functions contributes to SMA pathogenesis remains unknown. A shorter SMN isoform, axonal-SMN or a-SMN, with more specific axonal localization, has been discovered, but whether it might act in concert with FL-SMN in SMA pathogenesis is not known. As a first step in defining common or divergent intracellular roles of FL-SMN vs a-SMN proteins, we here characterized the turn-over of both proteins and investigated which pathway contributed to a-SMN degradation. We performed real time western blot and confocal immunofluorescence analysis in easily controllable in vitro settings. We analyzed co-transfected NSC34 and HeLa cells and cell clones stably expressing both a-SMN and FL-SMN proteins after specific blocking of transcript or protein synthesis and inhibition of known intracellular degradation pathways. Our data indicated that whereas the stability of both FL-SMN and a-SMN transcripts was comparable, the a-SMN protein was characterized by a much shorter half-life than FL-SMN. In addition, as already demonstrated for FL-SMN, the Ub/proteasome pathway played a major role in the a-SMN protein degradation. We hypothesize that the faster degradation rate of a-SMN vs FL-SMN is related to the protection provided by the protein complex in which FL-SMN is assembled. The diverse a-SMN vs FL-SMN C-terminus may dictate different protein interactions and complex formation explaining the different localization and role in the neuronal compartment, and the lower expression and stability of a-SMN.

Dataset Information

Circadian phase-specific degradation of the F-box protein ZTL is mediated by the proteasome.

Publications

Circadian phase-specific degradation of the F-box protein ZTL is mediated by the proteasome.

Similar Datasets

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