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In the title compound, [Pt(C3H2O4)(C7H16N2O2)], the Pt atom is coordinated to two O and two N atoms in a square-planar arrangement. The two independent mol­ecules, which have very similar structures, are approximately related by pseudo-twofold screw-axis symmetry. The six-membered chelate ring in the leaving ligand assumes a conformation intermediate between the half-chair and boat forms. The seven-membered ring in the carrier ligand assumes a twist-chair conformation and the oxolane ring assumes an envelope conformation. The crystal packing consists of extensive hydrogen-bonding networks which form two-dimensional molecular layers, and there are weak van der Waals interactions between these layers. [ABSTRACT FROM AUTHOR]

Covalent conjugations of the SUMO-1 moiety on a target protein play important roles in the regulation of cellular protein function. SUMO-conjugation of PML is a regulatory step for PML nuclear body (PML-NB) formation, and HIPK2 is SUMO-conjugated and recruited into the PML-NBs. Although HIPK2 mutations (R861W and N951I) were found in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients, little is known about the underlying mechanisms by which HIPK2 mutations are associated with the pathogenesis of leukemia. Here we show that HIPK2 mutants found in AML and MDS patients are defective in SUMO-interacting motif (SIM) function. Due to defective SIM function, the HIPK2 mutants were not modified with SUMO-1, and not recruited to the PML-NBs. However, the HIPK2 mutants can normally bind to and phosphorylate AML1b. Therefore, the HIPK2 mutants can sequestrate the AML1 complex out of the PML-NBs, resulting in the disruption of AML1-mediated activation of target genes for myeloid differentiation. In addition, the differentiation of K562 blast cells was impaired by the expression of the HIPK2 SIM-defective mutants. These results suggest that HIPK2 targeting into the PML-NBs via the SIMs is crucial for HIPK2-mediated induction of myeloid differentiation, and is associated with AML pathogenesis., Competing Interests: None.

Autophagy is a cellular process by which damaged organelles and dysfunctional proteins are degraded. Morusin is an anti-cancer drug isolated from the root bark of Morus alba . Morusin induces apoptosis in human prostate cancer cells by reducing STAT3 activity. In this study, we examined whether morusin induces autophagy and also examined the effects of autophagy on the morusin-induced apoptosis. Morusin induces LC3-II accumulation and ULK1 activation in HeLa cells. In addition, we found that induction of ULK1 Ser317 phosphorylation and reduction of ULK1 Ser757 phosphorylation occurred simultaneously during morusin-induced autophagy. Consistently, morusin induces autophagy by activation of AMPK and inhibition of mTOR activity. Next, we investigated the role of autophagy in morusin-induced apoptosis. Inhibition of autophagy by treating cells with the 3-methyladenine (3-MA) autophagic inhibitor induces high levels of morusin-mediated apoptosis, while treatment of cells with morusin alone induces moderate levels of apoptosis. Cell survival was greatly reduced when cells were treated with morusin and 3-MA. Taken together, morusin induces autophagy, which is an impediment for morusin-induced apoptosis, suggesting combined treatment of morusin with an autophagic inhibitor would increase the efficacy of morusin as an anti-cancer drug.