246 research outputs found
Històries de por (II). L'ombra de Frankenstein és allargada
Abstract not availabl
The melanoma-associated antigen 1 (MAGEA1) protein stimulates the E3 ubiquitin-ligase activity of TRIM31 within a TRIM31-MAGEA1-NSE4 complex
The MAGE (Melanoma-associated antigen) protein family members are structurally related to each other by a MAGEhomology domain comprised of 2 winged helix motifs WH/A and WH/B. This family specifically evolved in placental mammals although single homologs designated NSE3 (non-SMC element) exist in most eukaryotes. NSE3, together with its partner proteins NSE1 and NSE4 form a tight subcomplex of the structural maintenance of chromosomes SMC5–6 complex. Previously, we showed that interactions of the WH/B motif of the MAGE proteins with their NSE4/EID partners are evolutionarily conserved (including the MAGEA1-NSE4 interaction). In contrast, the interaction of the WH/A motif of NSE3 with NSE1 diverged in the MAGE paralogs. We hypothesized that the MAGE paralogs acquired new RING-finger containing partners through their evolution and form MAGE complexes reminiscent of NSE1-NSE3-NSE4 trimers. In this work, we employed the yeast 2-hybrid system to screen a human RING-finger protein library against several MAGE baits. We identified a number of potential MAGE-RING interactions and confirmed several of them (MDM4, PCGF6, RNF166, TRAF6, TRIM8, TRIM31, TRIM41) in co-immunoprecipitation experiments. Among these MAGE-RING pairs, we chose to examine MAGEA1-TRIM31 in detail and showed that both WH/A and WH/B motifs of MAGEA1 bind to the coiled-coil domain of TRIM31 and that MAGEA1 interaction stimulates TRIM31 ubiquitin-ligase activity. In addition, TRIM31 directly binds to NSE4, suggesting the existence of a TRIM31-MAGEA1-NSE4 complex reminiscent of the NSE1-NSE3-NSE4 trimer. These results suggest that MAGEA1 functions as a co-factor of TRIM31 ubiquitin-ligase and that the TRIM31-MAGEA1-NSE4 complex may have evolved from an ancestral NSE1-NSE3-NSE4 complex
Preparing an unsupervised massive analysis of SPHERE high contrast data with the PACO algorithm
We aim at searching for exoplanets on the whole ESO/VLT-SPHERE archive with
improved and unsupervised data analysis algorithm that could allow to detect
massive giant planets at 5 au. To prepare, test and optimize our approach, we
gathered a sample of twenty four solar-type stars observed with SPHERE using
angular and spectral differential imaging modes. We use PACO, a new generation
algorithm recently developed, that has been shown to outperform classical
methods. We also improve the SPHERE pre-reduction pipeline, and optimize the
outputs of PACO to enhance the detection performance. We develop custom built
spectral prior libraries to optimize the detection capability of the ASDI mode
for both IRDIS and IFS. Compared to previous works conducted with more
classical algorithms than PACO, the contrast limits we derived are more
reliable and significantly better, especially at short angular separations
where a gain by a factor ten is obtained between 0.2 and 0.5 arcsec. Under good
observing conditions, planets down to 5 MJup, orbiting at 5 au could be
detected around stars within 60 parsec. We identified two exoplanet candidates
that require follow-up to test for common proper motion. In this work, we
demonstrated on a small sample the benefits of PACO in terms of achievable
contrast and of control of the confidence levels. Besides, we have developed
custom tools to take full benefits of this algorithm and to quantity the total
error budget on the estimated astrometry and photometry. This work paves the
way towards an end-to-end, homogeneous, and unsupervised massive re-reduction
of archival direct imaging surveys in the quest of new exoJupiters.Comment: Accepted for publication in A&
Interactions between the Nse3 and Nse4 Components of the SMC5-6 Complex Identify Evolutionarily Conserved Interactions between MAGE and EID Families
The SMC5-6 protein complex is involved in the cellular response to DNA damage. It is composed of 6-8 polypeptides, of which Nse1, Nse3 and Nse4 form a tight sub-complex. MAGEG1, the mammalian ortholog of Nse3, is the founding member of the MAGE (melanoma-associated antigen) protein family and Nse4 is related to the EID (E1A-like inhibitor of differentiation) family of transcriptional repressors.Using site-directed mutagenesis, protein-protein interaction analyses and molecular modelling, we have identified a conserved hydrophobic surface on the C-terminal domain of Nse3 that interacts with Nse4 and identified residues in its N-terminal domain that are essential for interaction with Nse1. We show that these interactions are conserved in the human orthologs. Furthermore, interaction of MAGEG1, the mammalian ortholog of Nse3, with NSE4b, one of the mammalian orthologs of Nse4, results in transcriptional co-activation of the nuclear receptor, steroidogenic factor 1 (SF1). In an examination of the evolutionary conservation of the Nse3-Nse4 interactions, we find that several MAGE proteins can interact with at least one of the NSE4/EID proteins.We have found that, despite the evolutionary diversification of the MAGE family, the characteristic hydrophobic surface shared by all MAGE proteins from yeast to humans mediates its binding to NSE4/EID proteins. Our work provides new insights into the interactions, evolution and functions of the enigmatic MAGE proteins
MAGE-A cancer/testis antigens inhibit MDM2 ubiquitylation function and promote increased levels of MDM4
Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically
An inner warp discovered in the disk around HD 110058 using VLT/SPHERE and HST/STIS
An edge-on debris disk was detected in 2015 around the young, nearby A0V star
HD 110058. The disk showed features resembling those seen in the disk of beta
Pictoris that could indicate the presence of a perturbing planetary-mass
companion in the system. We investigated new and archival scattered light
images of the disk in order to characterise its morphology and spectrum. In
particular, we analysed the disk's warp to constrain the properties of possible
planetary perturbers. Our work uses data from two VLT/SPHERE observations and
archival data from HST/STIS. We measured the morphology of the disk by
analysing vertical profiles along the length of the disk to extract the
centroid spine position and vertical height. We extracted the surface
brightness and reflectance spectrum of the disk. We detect the disk between 20
au (with SPHERE) and 150 au (with STIS), at a position angle of
159.60.6. Analysis of the spine shows an asymmetry between
the two sides of the disk, with a 3.40.9 warp between ~20 au
and 60 au. The disk is marginally vertically resolved in scattered light, with
a vertical aspect ratio of 9.30.7% at 45 au. The extracted reflectance
spectrum is featureless, flat between 0.95 micron and 1.1 micron, and red from
1.1 micron to 1.65 micron. The outer parts of the disk are also asymmetric with
a tilt between the two sides compatible with a disk made of forward-scattering
particles and seen not perfectly edge-on, suggesting an inclination of
<84. The presence of an undetected planetary-mass companion on an
inclined orbit with respect to the disk could explain the warp. The
misalignment of the inner parts of the disk with respect to the outer disk
suggests a warp that has not yet propagated to the outer parts of the disk,
favouring the scenario of an inner perturber as the origin of the warp.Comment: 17 pages, 15 figures, 3 tables; accepted for publication in A&
An imaged 15Mjup companion within a hierarchical quadruple system
Since 2019, the direct imaging B-star Exoplanet Abundance Study (BEAST) at
SPHERE@VLT has been scanning the surroundings of young B-type stars in order to
ascertain the ultimate frontiers of giant planet formation. Recently, the
Myr HIP 81208 was found to host a close-in (~50 au) brown dwarf
and a wider (~230 au) late M star around the central 2.6Msun primary. Alongside
the continuation of the survey, we are undertaking a complete reanalysis of
archival data aimed at improving detection performances so as to uncover
additional low-mass companions. We present here a new reduction of the
observations of HIP 81208 using PACO ASDI, a recent and powerful algorithm
dedicated to processing high-contrast imaging datasets, as well as more
classical algorithms and a dedicated PSF-subtraction approach. The combination
of different techniques allowed for a reliable extraction of astrometric and
photometric parameters. A previously undetected source was recovered at a short
separation from the C component of the system. Proper motion analysis provided
robust evidence for the gravitational bond of the object to HIP 81208 C.
Orbiting C at a distance of ~20 au, this 15Mjup brown dwarf becomes the fourth
object of the hierarchical HIP 81208 system. Among the several BEAST stars
which are being found to host substellar companions, HIP 81208 stands out as a
particularly striking system. As the first stellar binary system with
substellar companions around each component ever found by direct imaging, it
yields exquisite opportunities for thorough formation and dynamical follow-up
studies.Comment: 12 pages, 9 figures, 5 tables. Accepted for publication as a Letter
in Astronomy and Astrophysics, section 1. Letters to the Edito
Peering into the Young Planetary System AB Pic. Atmosphere, Orbit, Obliquity & Second Planetary Candidate
We aim to revisit the system AB Pic which has a known companion at the
exoplanet/ brown-dwarf boundary. We based this study on a rich set of
observations to investigate the companion's orbit and atmosphere. We composed a
spectrum of AB Pic b merging archival VLT/SINFONI K-band data, with published
spectra at J and H-band (SINFONI) and Lp-band (Magellan-AO), and photometric
measurements (HST and Spitzer). We modeled the spectrum with ForMoSA, based on
two atmospheric models: ExoREM and BT-SETTL13. We determined the orbital
properties of b fitting the astrometric measurements from NaCo (2003 and 2004)
and SPHERE (2015). The orbital solutions favor a semi-major axis of 190au
viewed edge-on. With Exo-REM, we derive a T of 170050K and surface
gravity of 4.50.3dex, consistent with previous works, and we report for
the first time a C/O ratio of 0.580.08 (solar). The posteriors are
sensitive to the wavelength interval and the family of models used. Given the
2.1hr rotation period and our vsin(i) of 73km/s, we estimate for the
first time the true obliquity to be 45 or 135deg, indicating a
significant misalignment between the planet's spin and orbit orientations.
Finally, the existence of a proper motion anomaly between the Hipparcos and
Gaia eDR3 compared to our SPHERE detection limits and adapted radial velocity
limits indicate the existence of a 6M inner planet orbiting from
2 to 10au (40-200mas). The possible existence of an inner companion, together
with the likely miss-alignment of the spin axis orientation, strongly favor a
formation path by gravitational instability or core accretion within a disk
closer inside followed by dynamical interactions. Confirmation and
characterization of planet c and access to a broader wavelength coverage for
planet b will be essential to probe the uncertainties associated with the
parameters.Comment: 17 pages, 13 Figures, 6 Tables. Accepted for publication in A&A (31
of October
hnRNP Q and PTB modulate the circadian oscillation of mouse Rev-erb α via IRES-mediated translation
The physiological and behavioral circadian rhythms of most creatures are controlled by a harmony of functional relationships between clock genes. In mammals, several core clock genes show rhythmic profiles of their mRNA and protein expression. Among them, Rev-erb α functions as a transcriptional repressor, affecting expression patterns of other clock genes. For the continuous and robust oscillation of the molecular clock system, the levels of Rev-erb α protein are expected to be tightly regulated with the correct timing. Here, we demonstrate that Rev-erb α has an internal ribosomal entry site (IRES) in its 5′ untranslated region. Furthermore, we demonstrate that heterogeneous nuclear ribonucleoprotein Q and polypyrimidine tract-binding protein (PTB) modulate the IRES-mediated translation of Rev-erb α. We suggest that the rhythmic binding affinity of hnRNP Q to the Rev-erb α IRES and the change in PTB cytosolic levels lead to maintenance of the oscillation profile of the Rev-erb α protein
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