RESEARCH HIGHLIGHTS
IN BRIEF
STEM CELLS
Promoting death
The pro-apoptotic protein ARTS (a splice variant of the
septin 4 gene) promotes cell death of hair follicle
stem cells (HFSCs) and thus contributes to wound healing
and epidermal homeostasis, according to this study.
The authors observed that mouse HFSCs lacking ARTS
showed enhanced colony-forming ability and resistance to
apoptosis. Moreover, Arts–/– mice showed increased wound
repair and tissue regeneration compared with wild-type mice,
and this phenotype depended on HFSCs, as confirmed by
lineage-tracing assays. ARTS is known to be an antagonist of
XIAP (X-linked inhibitor of apoptosis protein), an E3 ubiquitin
ligase that inhibits apoptosis by negatively regulating
caspases. Consistent with this, XIAP levels were increased in
Arts–/– mouse HFSCs. Notably, the enhanced wound repair
observed in Arts–/– mice was abolished with concomitant loss of
XIAP, indicating that XIAP acts as a target for the pro-apoptotic
function of ARTS.
ORIGINAL RESEARCH PAPER Fuchs, Y. et al. Sept4/ARTS regulates stem cell apoptosis
and skin regeneration. Science http://dx.doi.org/10.1126/science.1233029 (2013)
C E L L G R OW T H
TORC1 coordinates cell growth and morphology
Apical cell growth in budding yeast is inhibited by
polarization of the actin cytoskeleton, an effect that can
be mediated by mating pheromone. Goranov et al. now
show that this inhibition is achieved through regulation of
target of rapamycin complex 1 (TORC1), which integrates
environmental signals such as nutrient availability to control
growth. Pheromone-mediated downregulation of growth
was attenuated in cells carrying constitutively active TORC1
or following inactivation of the TORC1 inhibitor Iml1.
Moreover, pheromone treatment had downstream effects
consistent with inhibition of TORC1 signalling, as it promoted
nuclear export (rather than entry) of the transcription factor
Sfp1 concomitantly with actin polarization. Importantly,
pheromone-mediated reduction in cell growth and Sfp1
nuclear export were alleviated by deletion of the gene
encoding the formin Bni1, which is required for actin
polarization.
ORIGINAL RESEARCH PAPER Goranov, A. I. et al. Changes in cell morphology are
coordinated with cell growth through the TORC1 pathway. Curr. Biol. http://dx.doi.
org/10.1016/j.cub.2013.05.035 (2013)
T R A N S L AT I O N
Recycling ribosomes
After mRNA transcription, ribosomes undergo controlled
release and recycling of their components. In some cases,
however, ribosomes can reinitiate translation at nearby open
reading frames. Here, Pestova and colleagues use an in vitro
translation system to determine the specific combinations of
eukaryotic initiation factors (eIFs) that allow 40S mammalian
ribosomes to remain associated with mRNA and reinitiate
translation. Whereas the addition of eIF2, eIF3, eIF1, eIF1A
and Met-tRNAiMet promoted 40S bidirectional scanning for
a nearby open reading frame, the presence of eIF4F drove
scanning specifically in the 3ʹ direction. Mobility analysis
indicated that this ability to reinitiate translation might also
apply to 80S ribosomes. Moreover, the authors speculate that
several factors, including the relative availability of eIFs, might
influence the prevalence of reinitiation events in vivo.
ORIGINAL RESEARCH PAPER Skabkin, M. A. et al. Reinitiation and other unconventional
posttermination events during eukaryotic translation. Mol. Cell 51, 1–16 (2013)
NATURE REVIEWS | MOLECULAR CELL BIOLOGY
VOLUME 14 | AUGUST 2013
© 2013 Macmillan Publishers Limited. All rights reserved
RESEARCH HIGHLIGHTS
IN BRIEF
A U TO P H AGY
Eating up damaged lysosomes
Autophagosomes engulf cytosol or damaged organelles and
deliver them to lysosomes to be degraded and released as
nutrients. Hung et al. show here that damaged lysosomes
themselves are degraded in this way. They utilized a
photosensitizer that is targeted to lysosomes by endocytosis;
its light-mediated activation triggers the formation of
reactive oxygen species, and thus lysosomal membrane
permeabilization (LMP), with spatio-temporal precision.
Imaging experiments following LMP in HeLa cells revealed that
tagged versions of ubiquitin, the selective autophagy adaptor
p62 and the late autophagosome marker LC3 accumulated in
the illuminated (and thus damaged) region of lysosomes. The
authors also showed that the autophagic structures that are
triggered by LMP become mature autolysosomes. Thus, they
propose that damaged lysosomes are removed by a type of
organelle-specific autophagy that they term lysophagy.
ORIGINAL RESEARCH PAPER Hung, Y.-H. et al. Spatiotemporally controlled induction of
autophagy-mediated lysosome turnover. Nature Commun. http://dx.doi.org/10.1038/
ncomms3111 (2013)
P R O T E I N M E TA B O L I S M
Cytosolic aggregates impair nuclear degradation
Polyglutamine (polyQ)-expanded proteins form cytoplasmic
aggregates that interfere with cellular protein quality control
systems. Park et al. studied how polyQ proteins disrupt the
clearance of misfolded proteins by the ubiquitin–proteasome
system. They found that the degradation of a misfolded mutant
version of cytosolic carboxypeptidase fused to GFP (CG*),
which is normally degraded in the nucleus, was inhibited by
co-expression of polyQ proteins, and that CG* accumulated in
the cytoplasm. A quantitative interactome analysis revealed that
polyQ aggregates sequester the yeast Hsp40 chaperone Sis1p
(and one of its mammalian homologues, DNAJB1), and that this
causes impaired CG* degradation. Importantly, the authors show
that the function of Sis1p is to transport CG* from the cytoplasm
to the nucleus for degradation.
ORIGINAL RESEARCH PAPER Park, S.-H. et al. PolyQ proteins interfere with nuclear
degradation of cytosolic proteins by sequestering the Sis1p chaperone. Cell 154,
134–145 (2013)
C H R O M AT I N
Lysosomes help process chromatin in senescence
Cellular senescence involves chromatin remodelling, and
Ivanov et al. show here that an autophagy–lysosome pathway
contributes to this. They observed more cytoplasmic chromatin
fragments (CCFs) in senescent cells than in proliferating cells;
these were positive for the DNA damage marker γH2A.X and
the heterochromatic histone mark H3K27me3 (trimethylated
Lys27 of histone H3). Using time-lapse imaging they observed
that CCFs associated with these marks entered the cytoplasm
by ‘blebbing’ off the cell nucleus and that the integrity of
the nuclear envelope was compromised in senescent cells.
The authors also found that CCFs partially colocalize with
autophagy markers and that the level of a lysosomal protease
(cathepsin L) that cleaves histone H3 to produce histone H3cs1
was increased in senescent cells, along with H3cs1 levels.
The histone content of senescent cells was also reduced in
a lysosome-dependent manner. The authors conclude that
“autophagy and lysosomes contribute to the proteolytic
processing of histones in senescence.”
ORIGINAL RESEARCH PAPER Ivanov, A. et al. Lysosome-mediated processing of chromatin
in senescence. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201212110 (2013)
NATURE REVIEWS | MOLECULAR CELL BIOLOGY
VOLUME 14 | AUGUST 2013
© 2013 Macmillan Publishers Limited. All rights reserved