[期刊]最新 Cell
Analysis
Getting Up Close and Personal with Your Genome
L.Bonetta
Commentary
Science on the Streets of the Big Apple
B. Greene and P. Nurse
Previews
Insect Odorant Receptors: Channeling Scent
T.S. Ha and D.P.Smith
Chromatin Proteins Do Double Duty
S. Ercan and J.D.Lieb
Follow the Monomer
J.E.Bear
p53 Regulation Orchestrates the TGF-β Response
S. Piccolo
Forever Young: Death-Defying Neuroblasts
J.M. Chell and A.H.Brand
Plant Evolution: TALES of Development
L. Dolan
Review
Regulatory T Cells and Immune Tolerance
S. Sakaguchi, T. Yamaguchi, T. Nomura, and M. Ono
Snapshot
p53 Posttranslational Modifications
J.-P. Kruse and W. Gu
Articles
XPD Helicase Structures and Activities: Insights into the Cancer
and Aging Phenotypes from XPD Mutations
L. Fan, J.O. Fuss, Q.J. Cheng, A.S. Arvai, M. Hammel, V.A.
Roberts, P.K. Cooper, and J.A. Tainer
Structure of the DNA Repair Helicase XPD
H. Liu, J. Rudolf, K.A. Johnson, S.A. McMahon, M. Oke, L. Carter,
A.-M. McRobbie, S.E. Brown, J.H. Naismith, and M.F. White
XPD is an essential component of the transcription factor TFIIH, a
ten-subunit complex that plays a dual role in transcription
initiation and nucleotide excision repair. XPD is a 5' to 3'
helicase with an iron-sulfur cluster domain and is conserved from
archaea to humans. Mutations of the xpd gene cause strikingly
different genetic disorders such as cancer-promoting Xeroderma
pigmentosum or the aging disorders Cockayne syndrome and
Trichothiodystrophy. Here, both Fan et al. and Liu et al. report
the crystal structures of archaeal XPD, which, together with
extensive biochemical studies, provide both a molecular basis for
the mechanism of the enzyme and possible explanations of the wide
spectrum of pathology arising from mutation of the gene.
Genome-wide Analysis Reveals MOF as a Key Regulator of Dosage
Compensation and Gene Expression in Drosophila
J. Kind, J.M. Vaquerizas, P. Gebhardt, M. Gentzel, N.M. Luscombe,
P. Bertone, and A. Akhta
Dosage compensation in Drosophila is achieved by increasing gene
expression from the single X chromosome in males and requires the
Male Specific Lethal (MSL) complex. In this issue, Kind and
colleagues reveal that the MSL complex component MOF, a histone
acetyltransferase, plays an important role not only in the
regulation of the male X chromosome but also in autosomal gene
regulation in both sexes. Intriguingly, MOF binding differs
between dosage-compensated genes and non-dosage-compensated genes.
MOF binding is characterized by a bimodal distribution at
promoters and the 3' ends of dosage-compensated genes but is
restricted to promoters on autosomes and the female X chromosome.
Thus, differential localization of chromatin-modifying enzymes may
be a strategy for achieving multiple regulatory functions from
one protein.
Early Sexual Origins of Homeoprotein Heterodimerization and
Evolution of the Plant KNOX/BELL Family
J.-H. Lee, H. Lin, S. Joo, and U. Goodenough
Homeoprotein heterodimers control core developmental transitions
in animals and land plants, as well as the haploid-diploid sexual
transitions of fungi. Hence, the diversification of homeoprotein
combinations has presumably been crucial to the radiation of
eukaryotic lineages. Lee and colleagues show that two
homeoproteins called Gsm1 and Gsp1 in the unicellular green alga
Chlamydomonas heterodimerize to drive both the haploid-diploid
transition and meiosis. This suggests that homeoprotein
heterodimers act in an earlier lineage than previously known and
perhaps originated in a sexual context. Furthermore, the patterns
of homeoprotein gene-family retention, expansion, and loss from
algae to plants suggest a model for the origin of land plants from
algal progenitors.
Capping Protein Increases the Rate of Actin-Based Motility by
Promoting Filament Nucleation by the Arp2/3 Complex
O. Akin and R.D. Mullins
Actin filament networks control cell shape and motility. The
architecture of these networks is determined in part by the Arp2/3
complex that nucleates new actin filament growth from the side of
an existing filament, thereby creating branch structures. Akin
and Mullins now report that Capping Protein, which binds to the
growing end of filaments and terminates growth, promotes
Arp2/3-mediated filament nucleation and branching. The crosstalk
between initiation and termination of filament growth is due to
competition between Arp2/3 and growing filaments for actin
monomers. Factors that cap filament ends tip the balance in favor
of new filament nucleation. This effect of Capping Protein in
remodeling the architecture of actin networks could explain its
known role in promoting cell motility.
The Big Brain Aquaporin Is Required for Endosome Maturation and
Notch Receptor Trafficking
R. Kanwar and M.E. Fortini
The formation of many tissues and organs depends upon a few key
developmental signaling pathways, such as the Notch pathway.
Kanwar and Fortini now demonstrate that big brain (Bib), a member
of the aquaporin family of channel proteins, is required for
endosomal maturation and trafficking of activated Notch receptors
in Drosophila epithelial cells. The loss of Bib caused abnormal
endosomal morphology that was accompanied by an overaccumulation
of Notch, Delta, and other signaling molecules. It also resulted
in reduced intracellular trafficking of Notch to cell nuclei.
These findings reveal an unprecedented role for an aquaporin in
endosomal biogenesis.
Chk1 Suppresses a Caspase-2 Apoptotic Response to DNA Damage that
Bypasses p53, Bcl-2, and Caspase-3
S. Sidi, T. Sanda, R.D. Kennedy, A.T. Hagen, C.A. Jette, R.
Hoffmans, J. Pascual, S. Imamura, S. Kishi, J.F. Amatruda, J.P.
Kanki, D.R. Green, A.A. D'Andrea, and A.T. Look
DNA damage-induced cell death usually proceeds through
p53-mediated activation of the intrinsic (mitochondrial) apoptotic
pathway. In some settings, p53 can also recruit components of the
extrinsic ("death-receptor") apoptotic pathway. Both apoptotic
pathways are inhibited by Bcl-2 and converge on caspase-3
activation. Sidi et al. identify an apoptotic response to DNA
damage conserved from zebrafish to man that bypasses p53, Bcl-2,
and caspase-3 altogether. This pathway requires ATM, ATR, and
caspase-2 and is suppressed by the Chk1 kinase, a key regulator of
S and G2/M cell-cycle progression after DNA damage. When released
from Chk1 inhibition and stimulated by genomic damage, this new
pathway forces apoptosis in cells that harbor p53 mutations or
overexpress Bcl-2, two of the most common genetic alterations in
human cancer.
Ectodermal Factor Restricts Mesoderm Differentiation by Inhibiting
p53
N. Sasai, R. Yakura, D. Kamiya, Y. Nakazawa, and Y. Sasai
During early vertebrate embryogenesis, three germ layers are
formed from pluripotent cells at the onset of gastrulation. Sasai
et al. report that the zygotic zinc finger protein XFDL156 is an
essential nuclear factor that promotes ectodermal differentiation
from pluripotent cells in Xenopus. It was known that mesodermal
determination requires the cooperation between TGF-b signaling and
p53 activity. The authors now find that XFDL156 directly binds to
the p53 protein and attenuates the activation of p53 target
genes. This zygotic ectodermal factor therefore restricts
mesodermal differentiation by controlling the spatiotemporal
responsiveness of the cell to p53-dependent signals.
Temporal Transcription Factors and Their Targets Schedule the End
of Neural Proliferation in Drosophila
C. Maurange, L. Cheng, and A.P. Gould
Neural stem and progenitor cells need to be instructed to stop
dividing once sufficient numbers of neurons have been generated
during brain development. In Drosophila, neural stem cell-like
progenitors called neuroblasts express a series of transcription
factors that endow progeny neurons with different temporal
identities. Maurange et al. report that progression to the end of
this transcription factor series specifies the time at which
neuroblast divisions cease, either via cell-cycle exit or
apoptosis. They also identify four targets of the transcription
factor series that link progenitor aging to changes in neural
proliferation and cell identity. These findings uncover a timing
mechanism essential for both development and ending proliferation
in the developing central nervous system.
The MicroRNA miR-1 Regulates a MEF-2-Dependent Retrograde Signal
at Neuromuscular Junctions
D.J. Simon, J.M. Madison, A.L. Conery, K.L. Thompson-Peer, M.
Soskis, G.B. Ruvkun, J.M. Kaplan, and J.K. Kim
Coordinated changes in pre- and postsynaptic function are
essential for many aspects of circuit development, including
synapse formation and plasticity. Here Simon et al. show that the
conserved microRNA miR-1 acts to regulate aspects of both pre- and
postsynaptic function at C. elegans neuromuscular junctions.
miR-1 alters synaptic transmission by regulating a retrograde
synaptic signal from muscle that inhibits neurotransmitter release
from motor neurons. This retrograde signal is induced by the
activation of muscle nicotinic acetylcholine receptors (nAChRs).
miR-1 regulates both the mRNA of MEF-2, a transcription factor
required in the activation of nAChRs, as well as the mRNAs that
encode two subunits of nAChR, thus providing a mechanism for how
the intensity of retrograde signaling is adjusted.
Live Imaging of Neuronal Degradation by Microglia Reveals a Role
for v0-ATPase a1 in Phagosomal Fusion In Vivo
F. Peri and C. Nüsslein-Volhard
During brain development, neurons are generated in great excess
with the majority being eliminated via apoptosis. Clearance of the
dying cells must be fast and efficient, and this task is
performed by "professional" phagocytes called microglia. Peri and
Nüsslein-Volhard present in vivo imaging of microglia-digesting
neurons in the living zebrafish brain. The results show that the
v0-ATPase a1 subunit mediates fusion between phagosomes and
lysosomes during phagocytosis independent of its previously
well-characterized proton pump activity. By describing microglial
phagocytosis in real time in vivo, this study sheds light on the
mechanisms of microglial-mediated neuronal degeneration.
Errata
Self-Renewing Osteoprogenitors in Bone Marrow Sinusoids Can
Organize a Hematopoietic Microenvironment
B. Sacchetti, A. Funari, S. Michienzi, S. Di Cesare, S. Piersanti,
I. Saggio, E. Tagliafico, S. Ferrari,
P.G. Robey, M. Riminucci, and P. Bianco
Allosteric Regulation of Histidine Kinases by Their Cognate
Response Regulator Determines Cell Fate
R. Paul, T. Jaeger, S. Abel, I. Wiederkehr, M. Folcher, E.G.
Biondi, M.T. Laub, and U. Jenal
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