Sumoylation in Development and Differentiation
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abstract
Tissue morphogenesis is a fascinating aspect of developmental biology and regeneration of certain adult organs, and timely control of cellular differentiation is a key to these processes. During development, events interrupting cellular differentiation and leading to organ failure are embryonic lethal; likewise, perturbation of differentiation in regenerating tissues leads to dysfunction and disease. At the molecular level, cellular differentiation is orchestrated by a well-coordinated cascade of transcription factors (TFs) driving gene expression. Altering TF localization, stability, or activity can affect the sequential organization of the gene expression program and result in abnormal tissue morphogenesis. An accumulating body of evidence shows that SUMO modifies a large pool of TFs and alters their transcriptional activities, and that preventing SUMO conjugation to target proteins causes abnormal cellular differentiation. In addition, overall inhibition of the sumoylation system during embryogenesis causes lethality, inferring a critical role for SUMO in regulating normal development. Understanding the profound regulatory role of SUMO in different tissues may lead not only to a better understanding of development biology, stem cell linage control, and cellular differentiation, but also lead to the identification of new targets for drug therapy. Springer Science+Business Media B.V. 2009.
