Noncanonical function of Capicua as a growth termination signal in Drosophila oogenesis

Significance Capicua (Cic) is a conserved HMG-box transcriptional repressor and tumor suppressor regulated by receptor tyrosine kinase signaling. Here, we report that a highly conserved yet uncharacterized Cic isoform called Cic-L has both canonical and noncanonical functions in Drosophila oogenesis. The noncanonical function takes place in oocyte-associated germline cells, which grow through polyploidization until Cic-L halts their growth and allows them to empty their contents into the oocyte. Unexpectedly, this function does not critically depend on the characteristic HMG-box domain and is instead mediated by the unique Cic-L N-terminal module. In fact, this module appears to have originated before Cic proteins acquired an HMG-box, suggesting that it plays ancient, autonomous functions that may be conserved across metazoans.

[1]  Oriol Vinyals,et al.  Highly accurate protein structure prediction with AlphaFold , 2021, Nature.

[2]  P. Jat,et al.  Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype , 2021, Frontiers in Cell and Developmental Biology.

[3]  S. Shvartsman,et al.  Coupled oscillators coordinate collective germline growth. , 2021, Developmental cell.

[4]  Adam C. Martin,et al.  Dynamics of hydraulic and contractile wave-mediated fluid transport during Drosophila oogenesis , 2020, Proceedings of the National Academy of Sciences.

[5]  Huadong Liu,et al.  CIC Is a Mediator of the ERK1/2-DUSP6 Negative Feedback Loop , 2020, iScience.

[6]  Y. Takenaka,et al.  Targeted disruption of Pparγ1 promotes trophoblast endoreplication in the murine placenta , 2020, bioRxiv.

[7]  S. Shvartsman,et al.  Rapid Dynamics of Signal-Dependent Transcriptional Repression by Capicua. , 2020, Developmental cell.

[8]  D. J. McKay,et al.  Changes in chromatin accessibility ensure robust cell cycle exit in terminally differentiated cells , 2019, PLoS biology.

[9]  P. Stadler,et al.  Trichoplax genomes reveal profound admixture and suggest stable wild populations without bisexual reproduction , 2018, Scientific Reports.

[10]  G. Jiménez,et al.  The Capicua tumor suppressor: a gatekeeper of Ras signaling in development and cancer , 2018, Cell cycle.

[11]  Z. Paroush,et al.  Capicua controls Toll/IL-1 signaling targets independently of RTK regulation , 2018, Proceedings of the National Academy of Sciences.

[12]  Maxime W. C. Rousseaux,et al.  Loss of Capicua alters early T cell development and predisposes mice to T cell lymphoblastic leukemia/lymphoma , 2018, Proceedings of the National Academy of Sciences.

[13]  G. Jiménez,et al.  Inactivation of Capicua in adult mice causes T-cell lymphoblastic lymphoma , 2017, Genes & development.

[14]  Maxime W. C. Rousseaux,et al.  Disruption of the ATXN1–CIC complex causes a spectrum of neurobehavioral phenotypes in mice and humans , 2017, Nature Genetics.

[15]  G. Jiménez,et al.  A new mode of DNA binding distinguishes Capicua from other HMG-box factors and explains its mutation patterns in cancer , 2017, PLoS genetics.

[16]  S. Asthana,et al.  Inactivation of Capicua drives cancer metastasis , 2016, Nature Genetics.

[17]  A. Spradling,et al.  Mouse oocytes differentiate through organelle enrichment from sister cyst germ cells , 2016, Science.

[18]  K. McCall,et al.  Phagocytosis genes nonautonomously promote developmental cell death in the Drosophila ovary , 2016, Proceedings of the National Academy of Sciences.

[19]  G. Jiménez,et al.  EGFR/Ras Signaling Controls Drosophila Intestinal Stem Cell Proliferation via Capicua-Regulated Genes , 2015, PLoS genetics.

[20]  S. Heuvel,et al.  G1/S Inhibitors and the SWI/SNF Complex Control Cell-Cycle Exit during Muscle Differentiation , 2015, Cell.

[21]  Alan S. Futran,et al.  Mapping the binding interface of ERK and transcriptional repressor Capicua using photocrosslinking , 2015, Proceedings of the National Academy of Sciences.

[22]  Selene L. Fernandez-Valverde,et al.  Deep developmental transcriptome sequencing uncovers numerous new genes and enhances gene annotation in the sponge Amphimedon queenslandica , 2015, BMC Genomics.

[23]  T. Orr-Weaver.  When bigger is better: the role of polyploidy in organogenesis. , 2015, Trends in genetics : TIG.

[24]  S. Cohen,et al.  Regulation of Pattern Formation and Gene Amplification During Drosophila Oogenesis by the miR-318 microRNA , 2015, Genetics.

[25]  Z. Paroush,et al.  Origins of Context-Dependent Gene Repression by Capicua , 2015, PLoS genetics.

[26]  L. Stevens,et al.  Maternal control of the Drosophila dorsal–ventral body axis , 2014, Wiley interdisciplinary reviews. Developmental biology.

[27]  L. Cooley,et al.  Methods for studying oogenesis. , 2014, Methods.

[28]  B. Edgar,et al.  Endocycles: a recurrent evolutionary innovation for post-mitotic cell growth , 2014, Nature Reviews Molecular Cell Biology.

[29]  Guilhem Faure,et al.  Identification of hidden relationships from the coupling of Hydrophobic Cluster Analysis and Domain Architecture information , 2013, Bioinform..

[30]  Peter D. Adams,et al.  Lysosome-mediated processing of chromatin in senescence , 2013, The Journal of cell biology.

[31]  G. Jiménez,et al.  Kinetics of gene derepression by ERK signaling , 2013, Proceedings of the National Academy of Sciences.

[32]  Stanislav Y. Shvartsman,et al.  Torso RTK controls Capicua degradation by changing its subcellular localization , 2012, Development.

[33]  G. Jiménez,et al.  Mirror represses pipe expression in follicle cells to initiate dorsoventral axis formation in Drosophila , 2012, Development.

[34]  Z. Paroush,et al.  The Capicua repressor – a general sensor of RTK signaling in development and disease , 2012, Journal of Cell Science.

[35]  C. Shaw,et al.  Exercise and Genetic Rescue of SCA1 via the Transcriptional Repressor Capicua , 2011, Science.

[36]  H. Zoghbi,et al.  ATXN1 protein family and CIC regulate extracellular matrix remodeling and lung alveolarization. , 2011, Developmental cell.

[37]  Yuchen Jiao,et al.  Mutations in CIC and FUBP1 Contribute to Human Oligodendroglioma , 2011, Science.

[38]  Z. Paroush,et al.  Capicua DNA-binding sites are general response elements for RTK signaling in Drosophila , 2011, Development.

[39]  B. Edgar,et al.  A robust cell cycle control mechanism limits E2F-induced proliferation of terminally differentiated cells in vivo , 2010, The Journal of cell biology.

[40]  Jean M. Davidson,et al.  Endoreplication: polyploidy with purpose. , 2009, Genes & development.

[41]  Siegfried Roth,et al.  Symmetry breaking during Drosophila oogenesis. , 2009, Cold Spring Harbor perspectives in biology.

[42]  R. Bastock,et al.  Drosophila oogenesis , 2008, Current Biology.

[43]  G. Bosco,et al.  Chromosome Alignment and Transvection Are Antagonized by Condensin II , 2008, Science.

[44]  D. Catalucci,et al.  Jcb: Article , 2022 .

[45]  Nicholas H. Putnam,et al.  The Trichoplax genome and the nature of placozoans , 2008, Nature.

[46]  V. Shahin,et al.  Apoptosis leads to a degradation of vital components of active nuclear transport and a dissociation of the nuclear lamina , 2008, Proceedings of the National Academy of Sciences.

[47]  R. Margueron,et al.  Retinoblastoma tumor suppressor protein–dependent methylation of histone H3 lysine 27 is associated with irreversible cell cycle exit , 2007, The Journal of cell biology.

[48]  E. Baehrecke,et al.  Growth Arrest and Autophagy Are Required for Salivary Gland Cell Degradation in Drosophila , 2007, Cell.

[49]  M. Aladjem,et al.  The cyclin‐dependent kinase inhibitor Dacapo promotes replication licensing during Drosophila endocycles , 2007, The EMBO journal.

[50]  I. Hariharan,et al.  Capicua Regulates Cell Proliferation Downstream of the Receptor Tyrosine Kinase/Ras Signaling Pathway , 2007, Current Biology.

[51]  Z. Paroush,et al.  A MAPK docking site is critical for downregulation of Capicua by Torso and EGFR RTK signaling , 2007, The EMBO journal.

[52]  Janghoo Lim,et al.  ATAXIN-1 Interacts with the Repressor Capicua in Its Native Complex to Cause SCA1 Neuropathology , 2006, Cell.

[53]  H. Aburatani,et al.  Fusion between CIC and DUX4 up-regulates PEA3 family genes in Ewing-like sarcomas with t(4;19)(q35;q13) translocation. , 2006, Human molecular genetics.

[54]  T. Rebello,et al.  Capicua regulates follicle cell fate in the Drosophila ovary through repression of mirror , 2006, Development.

[55]  S. Beckendorf,et al.  Tec29 controls actin remodeling and endoreplication during invagination of the Drosophila embryonic salivary glands , 2005, Development.

[56]  C. David,et al.  Oogenesis in Hydra: nurse cells transfer cytoplasm directly to the growing oocyte. , 2005, Developmental biology.

[57]  T. Orr-Weaver,et al.  Developmental gene amplification: insights into DNA replication and gene expression. , 2005, Trends in genetics : TIG.

[58]  Adrian A Canutescu,et al.  Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. , 2005, Developmental cell.

[59]  B. Calvi,et al.  Drosophila double-parked is sufficient to induce re-replication during development and is regulated by cyclin E/CDK2 , 2004, Development.

[60]  Bruce Stillman,et al.  Deregulation of cyclin E in human cells interferes with prereplication complex assembly , 2004, The Journal of cell biology.

[61]  J. S. Britton,et al.  dMyc is required for larval growth and endoreplication in Drosophila , 2004, Development.

[62]  David Stein,et al.  Drosophila dMyc is required for ovary cell growth and endoreplication , 2004, Development.

[63]  C. Berg,et al.  The Drosophila female sterile mutation twin peaks is a novel allele of tramtrack and reveals a requirement for Ttk69 in epithelial morphogenesis. , 2003, Developmental biology.

[64]  D. Haber,et al.  salvador Promotes Both Cell Cycle Exit and Apoptosis in Drosophila and Is Mutated in Human Cancer Cell Lines , 2002, Cell.

[65]  G. Jiménez,et al.  EGFR signalling inhibits Capicua-dependent repression during specification of Drosophila wing veins. , 2002, Development.

[66]  Deborah J. Goff,et al.  Establishment of dorsal-ventral polarity of the Drosophila egg requires capicua action in ovarian follicle cells. , 2001, Development.

[67]  I. Royzman,et al.  Drosophila double parked: a conserved, essential replication protein that colocalizes with the origin recognition complex and links DNA replication with mitosis and the down-regulation of S phase transcripts. , 2000, Genes & development.

[68]  G. Jiménez,et al.  Relief of gene repression by torso RTK signaling: role of capicua in Drosophila terminal and dorsoventral patterning. , 2000, Genes & development.

[69]  A. Spradling,et al.  Cell cycle control of chorion gene amplification. , 1998, Genes & development.

[70]  C. Lehner,et al.  Continuous Cyclin E expression inhibits progression through endoreduplication cycles in Drosophila , 1998, Current Biology.

[71]  P. O’Farrell,et al.  Fluctuations in Cyclin E levels are required for multiple rounds of endocycle S phase in Drosophila , 1998, Current Biology.

[72]  A. Spradling,et al.  The Drosophila endocycle is controlled by Cyclin E and lacks a checkpoint ensuring S-phase completion. , 1996, Genes & development.

[73]  C. Berg,et al.  Mutations in the Drosophila gene bullwinkle cause the formation of abnormal eggshell structures and bicaudal embryos. , 1995, Development.

[74]  C. Lehner,et al.  Cyclin E controls S phase progression and its down-regulation during Drosophila embryogenesis is required for the arrest of cell proliferation , 1994, Cell.

[75]  Robert Walgate,et al.  Proliferation , 1985, Nature.