Zinc controls PML nuclear body formation through regulation of a paralog specific auto-inhibition in SUMO1.

SUMO proteins are important regulators of many key cellular functions in part through their ability to form interactions with other proteins containing SUMO interacting motifs (SIMs). One characteristic feature of all SUMO proteins is the presence of a highly divergent intrinsically disordered region at their N-terminus. In this study, we examine the role of this N-terminal region of SUMO proteins in SUMO-SIM interactions required for the formation of nuclear bodies by the promyelocytic leukemia (PML) protein (PML-NBs). We demonstrate that the N-terminal region of SUMO1 functions in a paralog specific manner as an auto-inhibition domain by blocking its binding to the phosphorylated SIMs of PML and Daxx. Interestingly, we find that this auto-inhibition in SUMO1 is relieved by zinc, and structurally show that zinc stabilizes the complex between SUMO1 and a phospho-mimetic form of the SIM of PML. In addition, we demonstrate that increasing cellular zinc levels enhances PML-NB formation in senescent cells. Taken together, these results provide important insights into a paralog specific function of SUMO1, and suggest that zinc levels could play a crucial role in regulating SUMO1-SIM interactions required for PML-NB formation and function.

Biocatalytic synthesis of planar chiral macrocycles.

Macrocycles can restrict the rotation of substituents through steric repulsions, locking in conformations that provide or enhance the activities of pharmaceuticals, agrochemicals, aroma chemicals, and materials. In many cases, the arrangement of substituents in the macrocycle imparts an element of planar chirality. The difficulty in predicting when planar chirality will arise, as well as the limited number of synthetic methods to impart selectivity, have led to planar chirality being regarded as an irritant. We report a strategy for enantio- and atroposelective biocatalytic synthesis of planar chiral macrocycles. The macrocycles can be formed with high enantioselectivity from simple building blocks and are decorated with functionality that allows one to further modify the macrocycles with diverse structural features.

Acetylation of SUMO1 Alters Interactions with the SIMs of PML and Daxx in a Protein-Specific Manner.

The interactions between SUMO proteins and SUMO-interacting motif (SIM) in nuclear bodies formed by the promyelocytic leukemia (PML) protein (PML-NBs) have been shown to be modulated by either phosphorylation of the SIMs or acetylation of SUMO proteins. However, little is known about how this occurs at the atomic level. In this work, we examined the role that acetylation of SUMO1 plays on its binding to the phosphorylated SIMs (phosphoSIMs) of PML and Daxx. Our results demonstrate that SUMO1 binding to the phosphoSIM of either PML or Daxx is dramatically reduced by acetylation at either K39 or K46. However, acetylation at K37 only impacts binding to Daxx. Structures of acetylated SUMO1 variants bound to the phosphoSIMs of PML and Daxx demonstrate that there is structural plasticity in SUMO-SIM interactions. The plasticity observed in these structures provides a robust mechanism for regulating SUMO-SIM interactions in PML-NBs using signaling generated post-translational modifications.

Correction to: The M-phase specific hyperphosphorylation of Staufen2 involved the cyclin-dependent kinase CDK1.

Following publication of the original article [1], the authors reported a change to one of the author names.

The M-phase specific hyperphosphorylation of Staufen2 involved the cyclin-dependent kinase CDK1.

BACKGROUND: Staufen2 (STAU2) is an RNA-binding protein involved in the post-transcriptional regulation of gene expression. This protein was shown to be required for organ formation and cell differentiation. Although STAU2 functions have been reported in neuronal cells, its role in dividing cells remains deeply uncharacterized. Especially, its regulation during the cell cycle is completely unknown. RESULTS: In this study, we showed that STAU2 isoforms display a mitosis-specific slow migration pattern on SDS-gels in all tested transformed and untransformed cell lines. Deeper analyses in hTert-RPE1 and HeLa cells further indicated that the slow migration pattern of STAU2 isoforms is due to phosphorylation. Time course studies showed that STAU2 phosphorylation occurs before prometaphase and terminates as cells exit mitosis. Interestingly, STAU2 isoforms were phosphorylated on several amino acid residues in the C-terminal half via the cyclin-dependent kinase 1 (Cdk1), an enzyme known to play crucial roles during mitosis. Introduction of phospho-mimetic or phospho-null mutations in STAU2 did not impair its RNA-binding capacity, its stability, its interaction with protein co-factors or its sub-cellular localization, suggesting that STAU2 phosphorylation in mitosis does not regulate these functions. Similarly, STAU2 phosphorylation is not likely to be crucial for cell cycle progression since expression of phosphorylation mutants in hTert-RPE1 cells did not impair cell proliferation. CONCLUSIONS: Altogether, these results indicate that STAU2 isoforms are phosphorylated during mitosis and that the phosphorylation process involves Cdk1. The meaning of this post-translational modification is still elusive.