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Cell Mol Life Sci. 2018 Apr;75(7):1285-1301. doi: 10.1007/s00018-017-2697-4. Epub 2017 Nov 2.

SUMOylation controls stem cell proliferation and regional cell death through Hedgehog signaling in planarians.

Author information

1
Department of Molecular and Cell Biology, University of California, 5200 North Lake Road, Merced, CA, 95343, USA.
2
Quantitative and Systems Biology Graduate Program, University of California, Merced, USA.
3
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
4
Department of Molecular and Cell Biology, University of California, 5200 North Lake Road, Merced, CA, 95343, USA. noviedo2@ucmerced.edu.
5
Quantitative and Systems Biology Graduate Program, University of California, Merced, USA. noviedo2@ucmerced.edu.
6
Health Sciences Research Institute, University of California, Merced, USA. noviedo2@ucmerced.edu.

Abstract

Mechanisms underlying anteroposterior body axis differences during adult tissue maintenance and regeneration are poorly understood. Here, we identify that post-translational modifications through the SUMO (Small Ubiquitin-like Modifier) machinery are evolutionarily conserved in the Lophotrocozoan Schmidtea mediterranea. Disruption of SUMOylation in adult animals by RNA-interference of the only SUMO E2 conjugating enzyme Ubc9 leads to a systemic increase in DNA damage and a remarkable regional defect characterized by increased cell death and loss of the posterior half of the body. We identified that Ubc9 is mainly expressed in planarian stem cells (neoblasts) but it is also transcribed in differentiated cells including neurons. Regeneration in Ubc9(RNAi) animals is impaired and associated with low neoblast proliferation. We present evidence indicating that Ubc9-induced regional cell death is preceded by alterations in transcription and spatial expression of repressors and activators of the Hedgehog signaling pathway. Our results demonstrate that SUMOylation acts as a regional-specific cue to regulate cell fate during tissue renewal and regeneration.

KEYWORDS:

Genomic instability; Patched; Rad51; Regeneration; Ubc9

PMID:
29098326
DOI:
10.1007/s00018-017-2697-4

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