CyclinD-CDK4/6 complexes phosphorylate CDC25A and regulate its stability.

The phosphatase CDC25A is a key regulator of cell cycle progression by dephosphorylating and activating cyclin-CDK complexes. CDC25A is an unstable protein expressed from G1 until mitosis. CDC25A overexpression, which can be caused by stabilization of the protein, accelerates the G1/S and G2/M transitions, leading to genomic instability and promoting tumorigenesis. Thus, controlling CDC25A protein levels by regulating its stability is a critical mechanism for timing cell cycle progression and to maintain genomic integrity. Herein, we show that CDC25A is phosphorylated on Ser40 throughout the cell cycle and that this phosphorylation is established during the progression from G1 to S phase. We demonstrate that CyclinD-CDK4/CDK6 complexes mediate the phosphorylation of CDC25A on Ser40 during G1 and that these complexes directly phosphorylate this residue in vitro. Importantly, we also find that CyclinD1-CDK4 decreases CDC25A stability in a ßTrCP-dependent manner and that Ser40 and Ser88 phosphorylations contribute to this regulation. Thus our results identify cyclinD-CDK4/6 complexes as novel regulators of CDC25A stability during G1 phase, generating a negative feedback loop allowing control of the G1/S transition.

Vertigo and upside down vision due to an infarct in the territory of the medial branch of the posterior inferior cerebellar artery caused by dissection of a vertebral artery.

A 48 year old woman developed an acute vestibular syndrome associated with upside down vision a few hours after minor cervical trauma. Magnetic resonance imaging showed an ischaemic lesion in the territory of the medial branch of the posterior inferior cerebellar artery. An arteriogram showed a dissection of the left extracranial vertebral artery.

[Partial interauricular block. Apropos of a case]. / Bloc interauriculaire partiel. A propos d'une observation.

An observation of an inter-auricular conduction disorder is reported. This disorder concerned the median part of the left atrium as shown by evidence provided by stepped oesophageal recordings, which suggest an auricular depolarisation normally descending in the upper part of the left atrium but abnormally retrograded into the lower part. This suggests that interauricular conduction is blocked at the median inter-auricular passage but that it occurs by the tract of Bachmann at the upper part of the left atrium and by retrograde passage to the lower part. On the surface electrocardiogram, the wave P is diphasic + - in D2, D3 and aVF, of normal duration with a normal PR space.

[Partial interatrial block due to a conduction defect of the preferential middle interatrial depolarization pathway]. / Bloc interauriculaire partiel par trouble de conduction de la voie de dépolarisation préférentielle interauriculaire moyenne.

The authors report the case of partial interatrial block arising in the mid zone of the left atrium as demonstrated by oesophageal recordings. These showed that atrial depolarisation descending normally in the superior part of the left atrium was abnormally retrograde in the inferior part; this suggests a block of the mid-interatrial pathway and conduction via Bachmann's pathway in the upper part of the left atrium and via a retrograde pathway in the inferior region. The surface ECG showed a P wave of normal duration which was diphasic in Leads III and aVF with a normal PR interval. In addition, endocavitary recordings in the inferior part of the right atrium showed the presence of preatrial potentials potentials during three ectopic complexes, the significance of which is uncertain.

[Bepridil and hyperkalemia. Discussion of a case]. / Bépridil et hyperkaliémie. Discussion d'un cas.

The authors report a case with typical bepridil-induced electrocardiographic changes. Although the serum potassium was normal, an infusion of potassium chloride caused the electrical abnormalities induced by bepridil to disappear.