We identified a mechanism of VEGF overexpression in liver and mesentery that promotes pathologic, but not physiologic, angiogenesis, via sequential and nonredundant functions of CPEB1 and CPEB4. Regulation of CPEB4 by CPEB1 and the CPEB4 autoamplification loop induces pathologic angiogenesis. Strategies to block the activities of CPEBs might be developed to treat chronic liver and other angiogenesis-dependent diseases.
PLoS One. 2015 Sep 23;10(9):e0138794. doi: 10.1371/journal.pone.0138794. eCollection 2015.
Global Analysis of CPEBs Reveals Sequential and Non-Redundant Functions in Mitotic Cell Cycle.
- Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
- 2
- Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
Abstract
CPEB
(Cytoplasmic Polyadenylation Element Binding) proteins are a family of
four RNA-binding proteins that regulate the translation of maternal
mRNAs controlling meiotic cell cycle progression. But CPEBs are not
limited to the transcriptionally silent germline; they are also
expressed, in various combinations, in somatic cells, yet their role in
regulation of mitosis-related gene expression is largely unknown.
Deregulation of CPEB1 and CPEB4 have been linked to tumor development. However, a systematic analysis addressing their requirements for the temporal regulation of mitotic gene expression has yet to be performed.
This study addresses the requirements of each of the four CPEBs for mitotic phase transitions, with a particular focus on cytoplasmic polyadenylation and translational regulation.
We demonstrate that CPEB3 is the only member dispensable for mitotic cell division, whereas the other three members, CPEB1, 2, and 4, are essential to successful mitotic cell division.
Thus, CPEB1 is required for prophase entry,
CPEB2 for metaphase and
CPEB4 for cytokinesis.
These three CPEBs have sequential non-redundant functions that promote the phase-specific polyadenylation and translational activation of CPE-regulated transcripts in the mitotic cell cycle.
Deregulation of CPEB1 and CPEB4 have been linked to tumor development. However, a systematic analysis addressing their requirements for the temporal regulation of mitotic gene expression has yet to be performed.
This study addresses the requirements of each of the four CPEBs for mitotic phase transitions, with a particular focus on cytoplasmic polyadenylation and translational regulation.
We demonstrate that CPEB3 is the only member dispensable for mitotic cell division, whereas the other three members, CPEB1, 2, and 4, are essential to successful mitotic cell division.
Thus, CPEB1 is required for prophase entry,
CPEB2 for metaphase and
CPEB4 for cytokinesis.
These three CPEBs have sequential non-redundant functions that promote the phase-specific polyadenylation and translational activation of CPE-regulated transcripts in the mitotic cell cycle.
- PMID:
- 26398195
- PMCID:
- PMC4580432
- DOI:
- 10.1371/journal.pone.0138794
- [Indexed for MEDLINE]
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