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SUMO, a heavyweight in the control of cell proliferation

In senescent cells, transcription factor sumoylation is maintained at a small group of genes involved in proliferation and hence may limit their expression contributing to the irreversible arrest of cell proliferation.

Sumoylation at chromatin governs coordinated repression of a transcriptional program essential for cell growth and proliferation.

Neyret-Kahn H(1), Benhamed M, Ye T, Le Gras S, Cossec JC, Lapaquette P, Bischof O, Ouspenskaia M, Dasso M, Seeler J, Davidson I, Dejean A.

Genome Res Oct 2013

July 26, 2013

In a collaborative study, researchers from the Pasteur Institute in Paris and Irwin Davidson’s team at the IGBMC reveal how post-translational modification of transcription factors by sumoylation coordinates the control of cell proliferation. This study is published on July 26 in the journal Genome Research.

Modification of proteins

Translation of genetic information in DNA involves transcription into mRNA and translation of the mRNA into proteins by the ribosome. Once synthesized however, proteins are not at the end of their journey. They are subjected to many so called 'post-translational modifications’ involving the addition of small molecules on their amino acid chain that modulate their activity. Sumoylation is one of these modifications involving addition of a small peptide of the SUMO family. Mainly studied for its effect on cellular localization transport of proteins, sumoylation is also present at chromatin where it appears to play a role in regulating gene expression.


SUMO, a key player in cell proliferation

Many transcription factors, proteins that bind DNA and control gene expression, are modified by sumoylation. In a new study, the groups of Anne Dejean from the Institut Pasteur in Paris and Irwin Davidson at the IGBMC studied the distribution of sumoylated transcriptions factors across the genome. The researchers found that they are enriched on genes involved in the control of cell proliferation. They demonstrate that sumoylation of transcription factors limits the expression of the genes they are linked to and thus shed new light on the important role of SUMO molecules in the control of cell proliferation.


From proliferation to senescence

Transcription factor sumoylation is not static throughout the life of the cell. Unexpectedly, sumoylation is lost at most genes in senescent cells. Transcription factors retain high levels of SUMO at only a small number of genes essential for cell division, coding for histones and tRNA. As senescence is characterized by an irreversible arrest of cell division, the senescent state acts as a barrier against the proliferation of tumor cells. The researchers show that the loss of transcription factor sumoylation is characteristic of the senescence state and may play a role in establishing and maintaining this protective condition against tumor formation.


SUMO, a small molecule with big effects

This study establishes for the first time a map of sumoylated proteins across the genome. The location of these small SUMO molecules reveals how they coordinate the expression of many genes involved in crucial processes such as cell proliferation. These results represent a significant advance in understanding the mechanisms involved in cellular senescence and the sumoylation process itself. It remains to be determined whether loss of sumoylation is involved in the establishment of the senescence state or its maintenance and if the phenomenon observed in this study is valid for all cell types.


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