1,258 research outputs found
ERK2 phosphorylation of serine 77 regulates Bmf pro-apoptotic activity
B-cell lymphoma 2 (Bcl-2) homology 3 (BH3)-only proteins represent a class of pro-apoptotic factors that neutralize pro-survival Bcl-2 proteins, and, in some cases, directly activate Bax. The mechanisms of control and the role of BH3-only proteins, such as Bcl-2 like protein 11 extra large and Bad are well studied. By contrast, relatively little is known about the regulation and role of Bcl-2 modifying factor (Bmf). The B-RAF oncogene is mutated in ∼8% of human tumors. We have previously shown that Bmf is upregulated at the transcript level and is required for apoptosis induced by targeting B-RAF signaling in tumor cells harboring mutant B-RAF. In this study, we show that Bmf is regulated at the post-translational level by mutant B-RAF-MEK-ERK2 signaling. Extracellular signal-regulated kinase (ERK2) directly phosphorylates Bmf on serine 74 and serine 77 residues with serine 77 being the predominant site. In addition, serine 77 phosphorylation reduces Bmf pro-apoptotic activity likely through a mechanism independent of altering Bmf localization to the mitochondria and/or interactions with dynein light chain 2 and the pro-survival proteins, B-cell lymphoma extra large, Bcl-2 and Mcl-1. These data identify a novel mode of regulation in Bmf that modulates its pro-apoptotic activity in mutant B-RAF tumor cells
DNA mediated chromatin pull-down for the study of chromatin replication
Chromatin replication involves duplicating DNA while maintaining epigenetic information. These processes are critical for genome stability and for preserving cell-type identity. Here we describe a simple experimental approach that allows chromatin to be captured and its content analysed after in vivo replication and labeling of DNA by cellular DNA polymerases. We show that this technique is highly specific and that proteins bound to the replicated DNA can be analyzed by both immunological techniques and large scale mass spectrometry. As proof of concept we have used this novel procedure to begin investigating the relationship between chromatin protein composition and the temporal programme of DNA replication in human cells. It is expected that this technique will become a widely used tool to address how chromatin proteins assemble onto newly replicated DNA after passage of a replication fork and how chromatin maturation is coupled to DNA synthesis
Oldest pathology in a tetrapod bone illuminates the origin of terrestrial vertebrates
The origin of terrestrial tetrapods was a key event in vertebrate evolution, yet how and when it occurred remains obscure, due to scarce fossil evidence. Here, we show that the study of palaeopathologies, such as broken and healed bones, can help elucidate poorly understood behavioural transitions such as this. Using high-resolution finite element analysis, we demonstrate that the oldest known broken tetrapod bone, a radius of the primitive stem tetrapod Ossinodus pueri from the mid-Viséan (333 million years ago) of Australia, fractured under a high-force, impact-type loading scenario. The nature of the fracture suggests that it most plausibly occurred during a fall on land. Augmenting this are new osteological observations, including a preferred directionality to the trabecular architecture of cancellous bone. Together, these results suggest that Ossinodus, one of the first large (>2m length) tetrapods, spent a significant proportion of its life on land. Our findings have important implications for understanding the temporal, biogeographical and physiological contexts under which terrestriality in vertebrates evolved. They push the date for the origin of terrestrial tetrapods further back into the Carboniferous by at least two million years. Moreover, they raise the possibility that terrestriality in vertebrates first evolved in large tetrapods in Gondwana rather than in small European forms, warranting a re-evaluation of this important evolutionary event
Measurement of Exclusive B Decays to Final States Containing a Charmed Baryon
Using data collected by the CLEO detector in the Upsilon(4S) region, we
report new measurements of the exclusive decays of B mesons into final states
of the type Lambda_c^+ p-bar n(pi), where n=0,1,2,3. We find signals in modes
with one, two and three pions and an upper limit for the two body decay
Lambda_c^+ pbar. We also make the first measurements of exclusive decays of B
mesons to Sigma_c p-bar n(pi), where n=0,1,2. We find signals in modes with one
and two pions and an upper limit for the two body decay Sigma_c p-bar.
Measurements of these modes shed light on the mechanisms involved in B decays
to baryons.Comment: 11 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to PR
Measurement of the Masses and Widths of the Sigma_c^++ and Sigma_c^0 Charmed Baryons
Using data recorded by the CLEO II and CLEO II.V detector configurations at
CESR, we report new measurements of the masses of the Sigma_c^{++} and
Sigma_c^0 charmed baryons, and the first measurements of their intrinsic
widths. We find M(Sigma_c^{++}) - M(Lambda_c^+) = 167.4 +- 0.1 +- 0.2 MeV,
Gamma(Sigma_c^{++}) = 2.3 +- 0.2 +- 0.3 MeV, and M(Sigma_c^0) - M(Lambda_c^+) =
167.2 +- 0.1 +- 0.2 MeV, Gamma(Sigma_c^0) = 2.5 +- 0.2 +- 0.3 MeV, where the
uncertainties are statistical and systematic, respectively.Comment: 9 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to PRD, Rapid
Communications. Reference [13] correcte
Evidence for the Decay
We present a search for the ``wrong-sign'' decay D0 -> K+ pi- pi+ pi- using 9
fb-1 of e+e- collisions on and just below the Upsilon(4S) resonance. This decay
can occur either through a doubly Cabibbo-suppressed process or through mixing
to a D0bar followed by a Cabibbo-favored process. Our result for the
time-integrated wrong-sign rate relative to the decay D0 -> K- pi+ pi- pi+ is
(0.0041 +0.0012-0.0011(stat.) +-0.0004(syst.))x(1.07 +-0.10)(phase space),
which has a statistical significance of 3.9 standard deviations.Comment: 9 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to PR
Hadronic Mass Moments in Inclusive Semileptonic B Meson Decays
We have measured the first and second moments of the hadronic mass-squared
distribution in B -> X_c l nu, for P(lepton) > 1.5 GeV/c. We find <M_X^2 -
M_D[Bar]^2> = 0.251 +- 0.066 GeV^2, )^2 > = 0.576 +- 0.170
GeV^4, where M_D[Bar] is the spin-averaged D meson mass.
From that first moment and the first moment of the photon energy spectrum in
b -> s gamma, we find the HQET parameter lambda_1 (MS[Bar], to order 1/M^3 and
beta_0 alpha_s^2) to be -0.24 +- 0.11 GeV^2. Using these first moments and the
B semileptonic width, and assuming parton-hadron duality, we obtain |V_cb| =
0.0404 +- 0.0013.Comment: 11 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to PR
Observation of Exclusive barB --> D(*) K*- Decays
We report the first observation of the exclusive decays \bar B\to
D^{(*)}K^{*-}, using 9.66 x 10^{6} B\bar{B} pairs collected at the \Upsilon(4S)
with the CLEO detector. We measure the following branching fractions: {\cal
B}(B^- -> D^0 K^{*-})=(6.1 +- 1.6 +-1.7)x10^{-4}, {\cal B}(\bar{B^0} ->
D^+K^{*-})=(3.7 +- 1.5 +- 1.0) x 10^{-4}, {\cal B}(\bar{B^0} ->
D^{*+}K^{*-})=(3.8 +- 1.3 +- 0.8) x 10^{-4} and {\cal B}(B^- --> D^{*0}
K^{*-})=(7.7 +- 2.2 +- 2.6) x 10^{-4}. The \bar B ->D^*K^{*-} branching ratios
are the averages of those corresponding to the 00 and 11 helicity states. The
errors shown are statistical and systematic, respectively.Comment: 9 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, Published in
Phys.Rev.Lett.88:101803,200
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