Colicin E3 enhances the oxidoreductive activity of guinea-pig leucocytes

Summary Colicin E3 increased the capacity of peritoneal exudate leucocytes to reduce iodo-nitro-tetrazolium-chloride to formazane. This effect was directly dependent on its concentration within the range 10³–10⁵ lethal units per cell. In control experiments, dectran C exerted no influence on the rate of this activity and colicin E3 did not convert INT to formazane.     

Regulation of Parkin E3 ubiquitin ligase activity

Parkin is an E3 ubiquitin ligase mutated in autosomal recessive juvenile Parkinson's disease. In addition, it is a putative tumour suppressor, and has roles outside its enzymatic activity. It is critical for mitochondrial clearance through mitophagy, and is an essential protein in most eukaryotes. As such, it is a tightly controlled protein, regulated through an array of external interactions with multiple proteins, posttranslational modifications including phosphorylation and S-nitrosylation, and self-regulation through internal associations. In this review, we highlight some of the recent studies into Parkin regulation and discuss future challenges for gaining a full molecular understanding of the regulation of Parkin E3 ligase activity.     

Antagonistic action of E and F series prostaglandins upon mineralocorticoid production by the human adrenal

Summary At long time intervals, the E and F prostaglandins exert antagonistic effects on aldosterone production in vitro. At short intervals the E prostaglandins tend to mimic the inhibitory effect of the PGF series.     

E3 ubiquitin ligase RNF13 involves spatial learning and assembly of the SNARE complex

Changes in the structure and number of synapses modulate learning, memory and cognitive disorders. Ubiquitin-mediated protein modification is a key mechanism for regulating synaptic activity, though the precise control of this process remains poorly understood. RING finger protein 13 (RNF13) is a recently identified E3 ubiquitin ligase, and its in vivo function remains completely unknown. We show here that genetic deletion of RNF13 in mice leads to a significant deficit in spatial learning as determined by the Morris water maze test and Y-maze learning test. At the ultrastructral level, the synaptic vesicle density was decreased and the area of the active zone was increased at hippocampal synapses of RNF13-null mice compared with those of wild-type littermates. We found no change in the levels of SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) complex proteins in the hippocampus of RNF13-null mice, but impaired SNARE complex assembly. RNF13 directly interacted with snapin, a SNAP-25-interacting protein. Interestingly, snapin was ubiquitinated by RNF13 via the lysine-29 conjugated polyubiquitin chain, which in turn promoted the association of snapin with SNAP-25. Consistently, we found an attenuated interaction between snapin and SNAP-25 in the RNF13-null mice. Therefore, these results suggest that RNF13 is involved in the regulation of the SNARE complex, which thereby controls synaptic function.     

The activity of ibenzmethyzin hydrochloride against the human transplantable tumours human epithelioma No. 3 and human adenoma No. 1

Zusammenfassung Eine kritische Bewertung der vonGrunberg undPrince publizierten Ergebnisse und eigene Versuche lassen an einer deutlichen cytostatischen Aktivität von Ibenzmethyzin-Hydrochlorid (Natulan®) gegenüber H.Ad. Nr. 1 zweifeln. Eine neue Methode zur Erfassung chemotherapeutischer Effekte an Transplantationstumoren in der Hamsterbackentasche wird vorgeschlagen.     

The activity of ibenzmethyzin hydrochloride against the human transplantable tumors human epithelioma No. 3 and human adenoma No. 1

Zusammenfassung Ibenzmethyzinhydrochlorid zeigte tumorhemmende Wirkung gegen Human Epithelioma No. 3 in Ratten, die mittels Bestrahlung und Cortison konditioniert waren, und in Hamstern gegen Human Adenoma No. 1.     

Effect of colicin E3 on leukemia cells P 388 in vitro

Summary Proliferation of murine leukemia cells P388 is stimulated by less than 1.0 mg/ml colicin E3, while being inhibited by higher concentrations. By 1.6 mg/ml colicin E3, uptake of thymidine into cold TCA-precipitable fraction is decreased by 59% during 24 h, uptake of uridine by 29%.     

Effect of colicin E3 on leukemia cells P388 in vitro.

Proliferation of murine leukemia cells P388 is stimulated by less than 1.0 mg/ml colicin E3, while being inhibited by higher concentrations. By 1.6 mg/ml colicin E3, uptake of thymidine into cold TCA-precipitable fraction is decreased by 59% during 24 h, uptake of uridine by 29%.     

Ube3a,the E3 ubiquitin ligase causing Angelman syndrome and linked to autism,regulates protein homeostasis through the proteasomal shuttle Rpn10

Ubiquitination, the covalent attachment of ubiquitin to a target protein, regulates most cellular processes and is involved in several neurological disorders. In particular, Angelman syndrome and one of the most common genomic forms of autism, dup15q, are caused respectively by lack of or excess of UBE3A, a ubiquitin E3 ligase. Its Drosophila orthologue, Ube3a, is also active during brain development. We have now devised a protocol to screen for substrates of this particular ubiquitin ligase. In a neuronal cell system, we find direct ubiquitination by Ube3a of three proteasome-related proteins Rpn10, Uch-L5, and CG8209, as well as of the ribosomal protein Rps10b. Only one of these, Rpn10, is targeted for degradation upon ubiquitination by Ube3a, indicating that degradation might not be the only effect of Ube3a on its substrates. Furthermore, we report the genetic interaction in vivo between Ube3a and the C-terminal part of Rpn10. Overexpression of these proteins leads to an enhanced accumulation of ubiquitinated proteins, further supporting the biochemical evidence of interaction obtained in neuronal cells.