Organizer restriction through modulation of Bozozok stability by the E3 ubiquitin ligase Lnx-like.
In: Nature Cell Biology, Jg. 11 (2009-09-01), Heft 9, S. 1121-1127
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Zugriff:
The organizer anchors the primary embryonic axis, and balance between dorsal (organizer) and ventral domains is fundamental to body patterning. LNX (ligand of Numb protein-X) is a RING finger and four PDZ domain-containing E3 ubiquitin ligase. LNX serves as a binding platform and may have a role in cell fate determination, but its in vivo functions are unknown. Here we show that Lnx-l (Lnx-like) functions as a critical regulator of dorso-ventral axis formation in zebrafish. Depletion of Lnx-l using specific antisense morpholinos (MOs) caused strong embryonic dorsalization. We identified Bozozok (Boz, also known as Dharma or Nieuwkoid) as a binding partner and substrate of Lnx-l. Boz is a homeodomain-containing transcriptional repressor induced by canonical Wnt signalling that is critical for dorsal organizer formation. Lnx-l induced K48-linked polyubiquitylation of Boz, leading to its proteasomal degradation in human 293T cells and in zebrafish embryos. Dorsalization induced by Boz overexpression was suppressed by raising the level of Lnx-l, but Lnx-l failed to counteract dorsalization caused by mutant Boz lacking a critical motif for Lnx-l binding. Furthermore, dorsalization induced by depletion of Lnx-l was alleviated by attenuation of Boz expression. We conclude that Lnx-l modulates Boz activity to prevent the invasion of ventral regions of the embryo by organizer tissue. These studies introduce a ubiquitin ligase, Lnx-l, as a balancing modulator of axial patterning in the zebrafish embryo. [ABSTRACT FROM AUTHOR]
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Titel: |
Organizer restriction through modulation of Bozozok stability by the E3 ubiquitin ligase Lnx-like.
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Autor/in / Beteiligte Person: | Ro, Hyunju ; Dawid, Igor B. |
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Zeitschrift: | Nature Cell Biology, Jg. 11 (2009-09-01), Heft 9, S. 1121-1127 |
Veröffentlichung: | 2009 |
Medientyp: | academicJournal |
ISSN: | 1465-7392 (print) |
DOI: | 10.1038/ncb1926 |
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