Xp95 is phosphorylated within the proline rich domain during Xenopus oocyte maturation

Xp95 is the Xenopus ortholog of a conserved family of scaffold proteins that have in common an N-terminal Bro1 domain and a C-terminal proline rich domain (PRD). The regulation of this protein family is poorly understood. We previously showed that Xp95 undergoes a phosphorylation-dependant gel mobility shift during meiotic maturation of Xenopus oocytes, the only natural biological system in which post-translational modifications of this family has been demonstrated. Here we characterized Xp95 phosphorylation via two approaches. First, we tested a series of Xp95 fragments for the ability to gel-shift during oocyte maturation, and found that a fragment containing amino acids 705-786 is sufficient to cause a gel-shift. This fragment is within the N-terminal region of Xp95's PRD (N-PRD). Second, we purified phosphorylated Xp95 and by mass spectrometry found that a 5080 Da peptide which maps to N-PRD (amino acids 706-756) contains two phosphorylation sites, one of which is T745, within the conserved CIN85 binding motif. By in vitro protein interaction assays, we that T745 is critical for CIN85/Xp95 interaction, and that Xp95 phosphorylation correlates with loss of binding to CIN85. We also show that an Alix fragment (amino acids 604-789) also undergoes a gel-shift during oocyte maturation and during colcemid-induced mitotic arrest of HeLa cells. These findings indicate that Xp95/Alix is phosphorylated on the PRD during M phase induction and that the PRD phosphorylation regulates partner protein interaction. ^

Leukemia-associated retinoic acid receptor α fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies

In acute promyelocytic leukemia (APL), the typical t(15;17) and the rare t(11;17) translocations express, respectively, the PML/RARα and PLZF/RARα fusion proteins (where RARα is retinoic acid receptor α). Herein, we demonstrate that the PLZF and PML proteins interact with each other and colocalize onto nuclear bodies (NBs). Furthermore, induction of PML expression by interferons leads to a recruitment of PLZF onto NBs without increase in the levels of the PLZF protein. PML/RARα and PLZF/RARα localize to the same microspeckled nuclear domains that appear to be common targets for the two fusion proteins in APL. Although PLZF/RARα does not affect the localization of PML, PML/RARα delocalizes the endogenous PLZF protein in t(15;17)-positive NB4 cells, pointing to a hierarchy in the nuclear targeting of these proteins. Thus, our results unify the molecular pathogenesis of APL with at least two different RARα gene translocations and stress the importance of alterations of PLZF and RARα nuclear localizations in this disease.

Retinoic acid induces proteasome-dependent degradation of retinoic acid receptor α (RARα) and oncogenic RARα fusion proteins

Analyzing the pathways by which retinoic acid (RA) induces promyelocytic leukemia/retinoic acid receptor α (PML/RARα) catabolism in acute promyelocytic leukemia (APL), we found that, in addition to caspase-mediated PML/RARα cleavage, RA triggers degradation of both PML/RARα and RARα. Similarly, in non-APL cells, RA directly targeted RARα and RARα fusions to the proteasome degradation pathway. Activation of either RARα or RXRα by specific agonists induced degradation of both proteins. Conversely, a mutation in RARα that abolishes heterodimer formation and DNA binding, blocked both RARα and RXRα degradation. Mutations in the RARα DNA-binding domain or AF-2 transcriptional activation region also impaired RARα catabolism. Hence, our results link transcriptional activation to receptor catabolism and suggest that transcriptional up-regulation of nuclear receptors by their ligands may be a feedback mechanism allowing sustained target-gene activation.

Steric sea-level variations inferred from combined Topex/Poseidon altimetry and GRACE gravimetry

In this study, we propose to estimate the steric sea-level variations over a < 2-year period (April 2002 through December 2003) by combining global mean sea level (GMSL) based on Topex/ Poseidon (T/P) altimetry with time-variable geoid averaged over the oceans, as observed by the GRACE (Gravity Recovery and Climate Experiment) satellite. In effect, altimetry-derived GMSL changes results from two contributions: Steric (thermal plus salinity) effects due to sea water density change and ocean mass change due to water exchange with atmosphere and continents. On the other hand, GRACE data over the oceans provide the ocean mass change component only. The paper first discusses the corrections to apply to the GRACE data. Then the steric contribution to the GMSL is estimated using GRACE and T/P data. Comparison with available thermal expansion based on in situ hydrographic data is performed.

Scènes et proverbs

Le fruit défendu.--La crise.--Rédemption.--Le pour et le contre.--Alix.--La partie de dames.--La clef d'or.

Lettres sur les principales maladies qui ont regne' dans les hopitaux de l'armie du roi, en Italie, pendant les annees 1734, 1735, & 1736 /

Mode of access: Internet.

Oeuvres de Messire Jacques-Benigne Bossuet, Evêque de Meaux ... : tome troisiéme.

Exposition de la doctrine de l'Eglise Catholique -- Histoire des variations des Eglises Protestantes.

Oeuvres de Messire Jacques-Benigne Bossuet, Evêque de Meaux ... : tome septiéme.

Mystici in tuto -- Schola in tuto -- Quietismus redivivus, admonitio praevia... [et al.]

Oeuvres de Messire Jacques-Benigne Bossuet, Evêque de Meaux ... : tome huitiéme.

Mode of access: Internet.

Oeuvres de Messire Jacques-Benigne Bossuet, Evêque de Meaux ... : tome dixiéme.

Mode of access: Internet.

Les Oeuvres de M. Boileau Despréaux avec des eclaircissemens historiques : Tome second.

Mode of access: Internet.

Traité de l'amour de Dieu : necessaire dans le sacrement de penitence suivant la doctrine du Concile de Trente /

Mode of access: Internet.

Oeuvres de Messire Jacques-Benigne Bossuet, Evêque de Meaux ... : tome quatriéme.

Défense de l'histoire des variations contre la réponse de M. Basnage ... -- Premier[-sixiéme] avertissement aux protestans sur les lettres du Ministre Jurieu contre l'histoire des variations -- Avertissement sur la conférence avec M. Claude, Ministre de Charenton sur les matières de l'Eglise -- Réflexions sur un écrit de M. Claude.

Oeuvres de Messire Jacques-Benigne Bossuet, Evêque de Meaux ... : tome neuviéme.

Mode of access: Internet.

Oeuvres de Messire Jacques-Benigne Bossuet, Evêque de Meaux ... : tome cinquiéme.

Traité de la communion sous les deux especes -- Instruction pastorale sur les promesses de l'Eglise -- Lettre pastorale aux nouveaux catholiques sur la communion paschale -- Lettre sur l'adoration de la Croix ... [et al.]