Emerging roles of the SUMO pathway in development

Abstract

Sumoylation is a reversible post-translational modification that targets a variety of proteins mainly within the nucleus, but also in the plasma membrane and cytoplasm of the cell. It controls diverse cellular mechanisms such as subcellular localization, protein-protein interactions, or transcription factor activity. In recent years, the use of several developmental model systems has unraveled many critical functions for the sumoylation system in the early life of diverse species. In particular, detailed analyses of mutant organisms in both the components of the SUMO pathway and their targets have established the importance of the SUMO system in early developmental processes, such as cell division, cell lineage commitment, specification, and/or differentiation. In addition, an increasing number of developmental proteins, including transcription factors and epigenetic regulators, have been identified as sumoylation substrates. Sumoylation acts on these targets through various mechanisms. For example, this modification has been involved in converting a transcription factor from an activator to a repressor or in regulating the localization and/or stability of numerous transcription factors. This review will summarize current information on the function of sumoylation in embryonic development in different species from yeast to mammals.

Synthesis and biological actions of diphosphoinositol phosphates (inositol pyrophosphates), regulators of cell homeostasis

“…The enormous quantity of genes discloses no doubt that protein phosphorylation is an event that controls and regulates most cellular processes and nearly every signal transduction (Manning et al , 2002a,b ;Ubersax and Ferrell , 2007 ). Numerous further PTMs range from the well-known protein glycosylation via SUMOylations (for a review see Lomeli and Vazquez , 2011 ) to the less familiar and apparently unique lysine hypusination of the eukaryotic translation initiation factor 5A (eIF5A) (Park , 2006 ).…”

“…The greatest problem in addition to confi rmation from other laboratories is the lack of proof of a reasonable stoichiometry of the modifi cation by a real determination of modifi cation stoichiometry, e.g., of pmols of [ 32 P]phosphate transferred from β [ 32 P]-PP-InsP 5 to a pmol of protein in interest, and no such experimental derivation is available from the papers published to date. Admittedly, e.g., for transient SUMOylations where SUMO is a type of ' catalyst ' , a rather low stoichiometry of modifi cation of a protein is suffi cient (Lomeli and Vazquez , 2011 ). However, for the proposed action model of a steric hindrance of protein-protein interaction by the pyrophosphorylation we recognize a problem with low modifi cation stoichiometry, because the majority of unmodifi ed target protein still could undergo protein-protein interaction.…”

SUMOylation Is Developmentally Regulated and Required for Cell Pairing during Conjugation in Tetrahymena thermophila

“…The resulting UBA2 conditional cell lines and wild-type CU428 strains were grown vegetatively and transferred into 10 ml of SPP medium at an initial concentration of 200 cells/ml with either 0.1 g/ml cadmium or no cadmium. At 0, 4,8,12,20,24, and 48 h after placement in growth medium, cells were fixed and scored using a hemocytometer. (B) ⌬SMT3 homozygous homokaryon progeny were lethal within 24 h, and therefore a different approach was used to generate a conditional mutant expressing SMT3.…”

“…The importance of SUMOylation in regulating critical processes in eukaryotes is reflected in its modification of proteins in processes such as maintenance of chromosome structure and segregation (7), cell cycle progression (8), and DNA repair mechanisms (9,10). Depletion of Smt3p in budding yeast results in a phenotype where they are unable to segregate their chromosomes and suffer from short spindles (11,12).…”

RpL22e, but not RpL22e-like-PA, is SUMOylated and localizes to the nucleoplasm ofDrosophilameiotic spermatocytes

“…32 Further, the SUMOylation pathway is critical at multiple stages of spermatogenesis in several species, including Drosophila (for a review, see ref. 33).…”