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- ArticleGli1‐induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1
- Aidong Zhou1,
- Kangyu Lin1,
- Sicong Zhang1,2,
- Li Ma1,3,
- Jianfei Xue1,
- Saint‐Aaron Morris1,
- Kenneth D Aldape4 and
- Suyun Huang (suhuang{at}mdanderson.org)*,1,2
- 1Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- 2Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA
- 3Department of Neuro‐oncology and Neurosurgery, National Clinical Research Center for Cancer, Tianjin Medical University Institute and Hospital, Tianjin, China
- 4MacFeeters Hamilton Centre for Neuro‐Oncology Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
- ↵*Corresponding author. Tel: +1 713 834 6232; Fax: +1 713 834 6257; E‐mail: suhuang{at}mdanderson.org
Inappropriate Hedgehog signaling drives cancer formation. This study identifies USP48 as a new regulator of Gli1 stability and function and provides evidence that the Gli1‐USP48 regulatory axis is required for glioma cell growth and tumorigenesis.
Synopsis
Inappropriate Hedgehog signaling drives cancer formation. This study identifies USP48 as a new regulator of Gli1 stability and function and provides evidence that the Gli1‐USP48 regulatory axis is required for glioma cell growth and tumorigenesis.
USP48 stabilizes Gli1 and promotes the expression of Gli1 downstream targets in glioma cells.
USP48 interacts with Gli1 and deubiquitinates Gli1 directly.
Hh signaling induces USP48 expression through transcriptional activation by Gli1.
Depletion of USP48 inhibits glioblastoma cell growth and tumorigenesis, and expression of USP48 correlates with Gil1 expression in glioblastomas.
- Received July 26, 2016.
- Revision received May 5, 2017.
- Accepted May 9, 2017.
- © 2017 The Authors
- Science & SocietyThe “Anthropocene”: neglects, misconceptions, and possible futuresThe term “Anthropocene” is often erroneously used, as it is not formally defined yet
The term “Anthropocene” is often erroneously used, as it is not formally defined yet
- Valentí Rull (vrull{at}ictja.csic.es)1
Despite its popularity in scientific and social media, the “Anthropocene” is a term and concept still under discussion and still not formally recognized as a new geologic epoch.
- © 2017 The Author
- News & ViewsEnzyme sub‐functionalization driven by regulation
The emergence of functional novelties during protein evolution has puzzled scientists for many years. Most proposed models focus on repeated duplication‐divergence cycles, but the entanglement of selection pressures acting on the control of transcriptional and enzymatic activity, for example, by metabolites, has not been addressed so far. In this issue of EMBO Reports, Noda‐Garcia et al [1] describe two glutamate dehydrogenase paralogs from Bacillus subtilis with very similar sequences and under two distinct modes of activity control. The functional divergence of these two enzymes during evolution is driven by an interlinked combination of differences between their enzymatic properties and their transcriptional regulation. This article thus illuminates another level of complexity in molecular evolution that may help understand the hitherto unexplained co‐existence of paralogous genes that at first sight appear to be functionally redundant.
See also: L Noda‐Garcia et al
A study in this issue shows how the co‐evolution of transcriptional and enzyme activity regulation contributes to the functional divergence of two Bacilli glutamate dehydrogenase paralogs.
- © 2017 The Authors
- ArticleA post‐translational modification switch controls coactivator function of histone methyltransferases G9a and GLP
- Coralie Poulard1,
- Danielle Bittencourt1,
- Dai‐Ying Wu1,
- Yixin Hu1,
- Daniel S Gerke1 and
- Michael R Stallcup (stallcup{at}usc.edu)*,1
- 1Department of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
- ↵*Corresponding author. Tel: +1 323 865 3852; E‐mail: stallcup{at}usc.edu
Cooperative coactivator activity of G9a and GLP with glucocorticoid receptor and HP1γ is regulated by adjacent methylation and phosphorylation on G9a and GLP, which control binding to HP1γ. G9a, GLP and HP1γ are required for glucocorticoid activation of genes that inhibit cell migration.
Synopsis
Cooperative coactivator activity of G9a and GLP with glucocorticoid receptor and HP1γ is regulated by adjacent methylation and phosphorylation on G9a and GLP, which control binding to HP1γ. G9a, GLP and HP1γ are required for glucocorticoid activation of genes that inhibit cell migration.
Methylated G9a and GLP nucleate a complex with HP1γ and glucocorticoid receptor.
HP1γ recruitment by methylated G9a/GLP is required for their coactivator function.
G9a/GLP phosphorylation by Aurora kinase inhibits HP1γ binding and coactivator action.
- Received February 10, 2017.
- Revision received May 10, 2017.
- Accepted May 16, 2017.
- © 2017 The Authors
- ArticleRtt101‐Mms1‐Mms22 coordinates replication‐coupled sister chromatid cohesion and nucleosome assembly
- Jingjing Zhang1,
- Di Shi1,
- Xiaoli Li1,
- Lin Ding1,
- Jun Tang2,
- Cong Liu3,
- Katsuhiko Shirahige4,
- Qinhong Cao1 and
- Huiqiang Lou (lou{at}cau.edu.cn)*,1
- 1Beijing Advanced Innovation Center for Food Nutrition and Human Health, State Key Laboratory of Agro‐Biotechnology, College of Biological Sciences, China Agricultural University, Beijing, China
- 2State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing, China
- 3Laboratory of Genomic Stability, West China Second University Hospital, Sichuan University, Chengdu, China
- 4Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan
- ↵*Corresponding author. Tel:/Fax: +86 10 62734504; E‐mail: lou{at}cau.edu.cn
Genetic and biochemical assays reveal a role of Cul4‐Ddb1 (yeast Rtt101‐Mms1) ubiquitin ligases in promoting Eco1‐catalyzed Smc3 acetylation and thus sister chromatid cohesion establishment during S phase, which is critical for maintaining chromosome stability.
Synopsis
Genetic and biochemical assays reveal a role of Cul4‐Ddb1 (yeast Rtt101‐Mms1) ubiquitin ligases in promoting Eco1‐catalyzed Smc3 acetylation and thus sister chromatid cohesion establishment during S phase, which is critical for maintaining chromosome stability.
RTT101, MMS1 and MMS22 are stronger dosage suppressors of eco1 temperature sensitive mutants than PCNA.
Efficient Smc3 acetylation requires both Mms22‐ and PCNA‐ mediated interactions with Eco1.
There is cross talk between two replication‐coupled events, nucleosome reassembly and sister chromatid cohesion establishment.
- Received December 13, 2016.
- Revision received May 3, 2017.
- Accepted May 8, 2017.
- © 2017 The Authors
- ArticleLooping‐out mechanism for resolution of replicative stress at telomeres
- Tianpeng Zhang1,2,
- Zepeng Zhang1,2,
- Feng Li1,
- Qian Hu1,2,
- Haiying Liu1,2,
- Mengfan Tang1,
- Wenbin Ma1,
- Junjiu Huang1,
- Zhou Songyang1,
- Yikang Rong1,
- Shichuan Zhang3,
- Benjamin PC Chen4 and
- Yong Zhao (zhaoy82{at}mail.sysu.edu.cn)*,1,2
- 1Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat‐sen University, Guangzhou, China
- 2Collaborative Innovation Center of High Performance Computing, National University of Defense Technology, Changsha, China
- 3Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu, China
- 4Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA
- ↵*Corresponding author. Tel: +86 203 994 3401; Fax: +86 203 933 2944; E‐mail: zhaoy82{at}mail.sysu.edu.cn
Replication stress in telomeric DNA is resolved by a “looping‐out” mechanism, in which Topo II excises the stalled fork from the genome, NHEJ cyclizes cut DNA into t‐circle‐tail structures, and broken telomeric DNA is re‐ligated.
Synopsis
Replication stress in telomeric DNA is resolved by a “looping‐out” mechanism, in which Topo II excises the stalled fork from the genome, NHEJ cyclizes cut DNA into t‐circle‐tail structures, and broken telomeric DNA is re‐ligated.
Replication stress induces the formation of extrachromosomal t‐circle‐tail DNA, which resembles a cyclized leading or lagging strand during telomere replication.
Inhibition of Topo II or NHEJ impairs t‐circle‐tail formation, leading to accumulation of stalled replication forks at telomeres.
Net loss of telomeric DNA caused by a looping‐out mechanism during resolving replication stress may accelerate replicative senescence and cell aging.
- Received December 23, 2016.
- Revision received April 29, 2017.
- Accepted May 8, 2017.
- © 2017 The Authors
- ArticleHigh‐affinity cooperative Ca2+ binding by MICU1–MICU2 serves as an on–off switch for the uniporter
- Kimberli J Kamer1,2,
- Zenon Grabarek (grabarek{at}molbio.mgh.harvard.edu)*,2 and
- Vamsi K Mootha (vamsi_mootha{at}hms.harvard.edu)*,2,3,4
- 1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA
- 2Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA
- 3Department of Systems Biology, Harvard Medical School, Boston, MA, USA
- 4Broad Institute, Cambridge, MA, USA
- ↵*
Corresponding author. Tel: +1 617 724 3151; E‐mail: grabarek{at}molbio.mgh.harvard.edu
Corresponding author. Tel: +1 617 643 3059; E‐mail: vamsi_mootha{at}hms.harvard.edu
The MICU1–MICU2 heterodimer binds Ca2+ cooperatively with high affinity, which sets a sharp threshold for the uniporter, and allows direct response to cytosolic Ca2+ signals. Interaction with cardiolipin facilitates tethering of MICU1–MICU2 to the inner membrane.
Synopsis
The MICU1–MICU2 heterodimer binds Ca2+ cooperatively with high affinity, which sets a sharp threshold for the uniporter, and allows direct response to cytosolic Ca2+ signals. Interaction with cardiolipin facilitates tethering of MICU1–MICU2 to the inner membrane.
MICU1 and MICU2 form a heterodimer, which binds Ca2+ with 620 nM affinity.
MICU1–MICU2 Ca2+ binding determines the threshold of the mitochondrial uniporter.
MICU1 and MICU2 bind cardiolipin irrespective of Ca2+, tethering the complex to the inner membrane.
- Received December 1, 2016.
- Revision received May 1, 2017.
- Accepted May 4, 2017.
- © 2017 The Authors
