Nuclear accumulation of ZFP36L1 is cell cycle-dependent and determined by a C-terminal serine-rich cluster
Autor: | Shunsuke Sakai, Yuki Matsuura, Aya Noguchi, Naoto Yokota, Hiroyuki Kawahara |
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Rok vydání: | 2020 |
Předmět: |
RNA Stability
Nuclear Localization Signals Uterine Cervical Neoplasms RNA-binding protein Biochemistry 03 medical and health sciences 0302 clinical medicine Protein Domains Serine medicine Humans ZFP36 Nuclear export signal Molecular Biology 030304 developmental biology Cell Nucleus 0303 health sciences Chemistry Cell Cycle General Medicine Cell cycle Cell biology Cell nucleus medicine.anatomical_structure Cytoplasm Female Butyrate Response Factor 1 Nucleus 030217 neurology & neurosurgery Nuclear localization sequence HeLa Cells |
Zdroj: | The Journal of Biochemistry. 168:477-489 |
ISSN: | 1756-2651 0021-924X |
DOI: | 10.1093/jb/mvaa072 |
Popis: | ZFP36L1 is an RNA-binding protein responsible for mRNA decay in the cytoplasm. ZFP36L1 has also been suggested as a nuclear-cytoplasmic shuttling protein because it contains a potential nuclear localization signal and a nuclear export signal. However, it remains unclear how the nuclear localization of ZFP36L1 is controlled. In this study, we provide evidence that the nuclear accumulation of ZFP36L1 protein is modulated in a cell cycle-dependent manner. ZFP36L1 protein accumulation in fractionated nuclei was particularly prominent in cells arrested at G1-/S-phase boundary, while it was downregulated in S-phase cells, and eventually disappeared in G2-phase nuclei. Moreover, forced nuclear targeting of ZFP36L1 revealed marked downregulation of this protein in S- and G2-phase cells, suggesting that ZFP36L1 can be eliminated in the nucleus. The C-terminal serine-rich cluster of ZFP36L1 is critical for the regulation of its nuclear accumulation because truncation of this probable disordered region enhanced the nuclear localization of ZFP36L1, increased its stability and abolished its cell cycle-dependent fluctuations. These findings provide the first hints to the question of how ZFP36L1 nuclear accumulation is controlled during the course of the cell cycle. |
Databáze: | OpenAIRE |
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