UK research funding - p363

doi:10.1038/ncb0409-363a

Is the UK still committed to basic biology research?

Full Text - UK research funding | PDF (128 KB) - UK research funding

Turning points - p363

doi:10.1038/ncb0409-363b

A series of essays describing pivotal events in the careers of cell biologists.

Full Text - Turning points | PDF (128 KB) - Turning points

Coming in from the cold: how answering a postcard can launch a scientific career - p364

Gottfried Schatz

doi:10.1038/ncb0409-364

Full Text - Coming in from the cold: how answering a postcard can launch a scientific career | PDF (105 KB) - Coming in from the cold: how answering a postcard can launch a scientific career

Spindle orientation during asymmetric cell division - pp365 - 374

Karsten H. Siller & Chris Q. Doe

doi:10.1038/ncb0409-365

Abstract - Spindle orientation during asymmetric cell division | Full Text - Spindle orientation during asymmetric cell division | PDF (2,278 KB) - Spindle orientation during asymmetric cell division

Double JMY: making actin fast - pp375 - 376

David W. Roadcap & James E. Bear

doi:10.1038/ncb0409-375

The assembly of actin networks is dependent on nucleation-promoting factors. A new study identifies JMY as a protein containing two separate nucleation-promoting activities that shuttles between the nucleus and the cytoplasm and promotes cell migration. These observations indicate that JMY is an important factor controlling actin dynamics in motile cells.

Full Text - Double JMY: making actin fast | PDF (172 KB) - Double JMY: making actin fast

See also: Letter by Zuchero et al.

Skp2: caught in the Akt - pp377 - 379

Karin Ecker & Ludger Hengst

doi:10.1038/ncb0409-377

To control cell proliferation, signal transduction needs to regulate the cell-cycle machinery. Recent findings show that Akt — a major kinase that coordinates diverse signalling pathways — phosphorylates Skp2, a subunit of the SCF-Skp2 ubiquitin ligase that targets key cell-cycle regulators. Akt1-dependent phosphorylation activates SCF-Skp2 through multiple mechanisms.

Full Text - Skp2: caught in the Akt | PDF (241 KB) - Skp2: caught in the Akt

See also: Article by Lin et al. | Article by Gao et al.

Targeting protein ubiquitylation: DDB1 takes its RING off - pp379 - 381

Sarah Jackson & Yue Xiong

doi:10.1038/ncb0409-379

Ubiquitin E3 ligases of the RING and HECT families are distinct not only in their catalytic mechanisms but also in targeting substrates. Now it seems that one heterodimeric complex can target substrates to both types of E3 ligase.

Full Text - Targeting protein ubiquitylation: DDB1 takes its RING off | PDF (187 KB) - Targeting protein ubiquitylation: DDB1 takes its RING off

See also: Article by Maddika & Chen

SOC: now also store-operated cyclase - pp381 - 382

James W. Putney, Jr

doi:10.1038/ncb0409-381

Depletion of Ca²⁺ from intracellular stores has long been known to signal to and activate plasma membrane 'store-operated' channels. We now learn that store depletion also controls the formation of cyclic AMP (cAMP) through the regulation of adenylyl cyclase (A-Cyclase). These findings substantially broaden the scope and biological significance of Ca²⁺ store-regulated signalling.

Full Text - SOC: now also store-operated cyclase | PDF (219 KB) - SOC: now also store-operated cyclase

See also: Article by Lefkimmiatis et al.

Research highlights - p383

doi:10.1038/ncb0409-383

Full Text - Research highlights | PDF (107 KB) - Research highlights

Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages - pp385 - 396

Kohichi Matsunaga, Tatsuya Saitoh, Keisuke Tabata, Hiroko Omori, Takashi Satoh, Naoki Kurotori, Ikuko Maejima, Kanae Shirahama-Noda, Tohru Ichimura, Toshiaki Isobe, Shizuo Akira, Takeshi Noda & Tamotsu Yoshimori

doi:10.1038/ncb1846

Beclin 1 is an essential mediator of mammalian autophagy that has anti-tumour activity. Beclin 1 associates with Atg14L and Rubicon to regulate autophagosome formation and maturation, respectively.

Abstract - Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages | Full Text - Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages | PDF (8,405 KB) - Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages | Supplementary information

Phosphorylation by Akt1 promotes cytoplasmic localization of Skp2 and impairs APCCdh1-mediated Skp2 destruction - pp397 - 408

Daming Gao, Hiroyuki Inuzuka, Alan Tseng, Rebecca Y. Chin, Alex Toker & Wenyi Wei

doi:10.1038/ncb1847

Skp2 is a known component of the SCF ubiquitin ligase that targets the cell-cycle regulator p27. Akt kinase phosphorylates Skp2 and regulates its stability and cytoplasmic localization.

Abstract - Phosphorylation by Akt1 promotes cytoplasmic localization of Skp2 and impairs APCCdh1-mediated Skp2 destruction | Full Text - Phosphorylation by Akt1 promotes cytoplasmic localization of Skp2 and impairs APCCdh1-mediated Skp2 destruction | PDF (6,129 KB) - Phosphorylation by Akt1 promotes cytoplasmic localization of Skp2 and impairs APCCdh1-mediated Skp2 destruction | Supplementary information

See also: News and Views by Ecker & Hengst

Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3 ligase - pp409 - 419

Subbareddy Maddika & Junjie Chen

doi:10.1038/ncb1848

The kinase DYRK2 regulates the assembly of a ubiquitin ligase complex in a phosphorylation-independent manner, while also phosphorylating the target for the ligase. Thus, ligase assembly and target ubiquitylation appear to be physically linked processes.

Abstract - Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3 ligase | Full Text - Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3 ligase | PDF (2,213 KB) - Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3 ligase | Supplementary information

See also: News and Views by Jackson & Xiong

Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB - pp420 - 432

Hui-Kuan Lin, Guocan Wang, Zhenbang Chen, Julie Teruya-Feldstein, Yan Liu, Chia-Hsin Chan, Wei-Lei Yang, Hediye Erdjument-Bromage, Keiichi I. Nakayama, Stephen Nimer, Paul Tempst & Pier Paolo Pandolfi

doi:10.1038/ncb1849

Skp2 is a known component of the SCF ubiquitin ligase that ubiquitylates the cell-cycle regulator p27. Akt kinase directly phosphorylates Skp2 and regulates SCF complex assembly and ligase activity, Skp2 cytoplasmic localization and Skp2-dependent regulation of cell proliferation and migration.

Abstract - Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB | Full Text - Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB | PDF (3,767 KB) - Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB | Supplementary information

See also: News and Views by Ecker & Hengst

Store-operated cyclic AMP signalling mediated by STIM1 - pp433 - 442

Konstantinos Lefkimmiatis, Meera Srikanthan, Isabella Maiellaro, Mary Pat Moyer, Silvana Curci & Aldebaran M. Hofer

doi:10.1038/ncb1850

The ER Ca²⁺ sensor protein STIM1 regulates cAMP signalling by coupling the changes in luminal ER Ca²⁺ content to adenylyl cyclase activity.

Abstract - Store-operated cyclic AMP signalling mediated by STIM1 | Full Text - Store-operated cyclic AMP signalling mediated by STIM1 | PDF (1,333 KB) - Store-operated cyclic AMP signalling mediated by STIM1 | Supplementary information

See also: News and Views by Putney

Myosin IIIa boosts elongation of stereocilia by transporting espin 1 to the plus ends of actin filaments - pp443 - 450

Felipe T. Salles, Raymond C. Merritt, Jr, Uri Manor, Gerard W. Dougherty, Aurea D. Sousa, Judy E. Moore, Christopher M. Yengo, Andréa C. Dosé & Bechara Kachar

doi:10.1038/ncb1851

Actin filaments in stereocilia on the surface of inner ear sensory hair cells are continually renewed. Myosin IIIa transports the actin-binding/bundling protein espin to stereocilia tips and cooperates with espin in actin filament elongation.

First Paragraph - Myosin IIIa boosts elongation of stereocilia by transporting espin 1 to the plus ends of actin filaments | Full Text - Myosin IIIa boosts elongation of stereocilia by transporting espin 1 to the plus ends of actin filaments | PDF (2,461 KB) - Myosin IIIa boosts elongation of stereocilia by transporting espin 1 to the plus ends of actin filaments | Supplementary information

p53-cofactor JMY is a multifunctional actin nucleation factor - pp451 - 459

J. Bradley Zuchero, Amanda S. Coutts, Margot E. Quinlan, Nicholas B. La Thangue & R. Dyche Mullins

doi:10.1038/ncb1852

JMY, originally discovered as a binding partner of the p53 co-activator p300, is an actin-nucleating protein, assembling filaments both by activation of the Arp2/3 complex and through an Arp2/3-independent mechanism.

First Paragraph - p53-cofactor JMY is a multifunctional actin nucleation factor | Full Text - p53-cofactor JMY is a multifunctional actin nucleation factor | PDF (3,423 KB) - p53-cofactor JMY is a multifunctional actin nucleation factor | Supplementary information

See also: News and Views by Roadcap & Bear

Characterization of the interface between normal and transformed epithelial cells - pp460 - 467

Catherine Hogan, Sophie Dupré-Crochet, Mark Norman, Mihoko Kajita, Carola Zimmermann, Andrew E. Pelling, Eugenia Piddini, Luis Alberto Baena-López, Jean-Paul Vincent, Yoshifumi Itoh, Hiroshi Hosoya, Franck Pichaud & Yasuyuki Fujita

doi:10.1038/ncb1853

How a transformed cell interacts with normal cells remains unclear. Most RasV12-transformed cells in an epithelial monolayer are extruded apically in a manner regulated by ROCK, Myosin II and Cdc42, but some cells invade the basal matrix via a mechanism requiring PI3 kinase.

Abstract - Characterization of the interface between normal and transformed epithelial cells | Full Text - Characterization of the interface between normal and transformed epithelial cells | PDF (4,791 KB) - Characterization of the interface between normal and transformed epithelial cells | Supplementary information

Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1–phosphatidylinositol-3-kinase complex - pp468 - 476

Yun Zhong, Qing Jun Wang, Xianting Li, Ying Yan, Jonathan M. Backer, Brian T. Chait, Nathaniel Heintz & Zhenyu Yue

doi:10.1038/ncb1854

Beclin 1 is an essential mediator of mammalian autophagy that has anti-tumour activity. Two proteins that interact with Beclin 1 have been newly identified and their analysis shows that distinct Beclin 1 complexes regulate autophagosome formation and maturation, respectively.

First Paragraph - Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex | Full Text - Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1–phosphatidylinositol-3-kinase complex | PDF (3,855 KB) - Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1–phosphatidylinositol-3-kinase complex | Supplementary information

A mechanism for chromosome segregation sensing by the NoCut checkpoint - pp477 - 483

Manuel Mendoza, Caren Norden, Kathrin Durrer, Harald Rauter, Frank Uhlmann & Yves Barral

doi:10.1038/ncb1855

In yeast, anaphase defects can trigger activation of the NoCut checkpoint, resulting in delayed cytokinesis. The Ilp1/aurora kinase localizes to the spindle midzone and monitors chromatin segregation, thus acting as a chromatin sensor.

First Paragraph - A mechanism for chromosome segregation sensing by the NoCut checkpoint | Full Text - A mechanism for chromosome segregation sensing by the NoCut checkpoint | PDF (1,246 KB) - A mechanism for chromosome segregation sensing by the NoCut checkpoint | Supplementary information

Modularity of MAP kinases allows deformation of their signalling pathways - pp484 - 491

Areez Mody, Joan Weiner & Sharad Ramanathan

doi:10.1038/ncb1856

During evolution, MAP kinases repeatedly changed substrate specificities and interaction partners. Because of their modular design, they can be experimentally re-designed to achieve rewiring of the signalling network.

First Paragraph - Modularity of MAP kinases allows deformation of their signalling pathways | Full Text - Modularity of MAP kinases allows deformation of their signalling pathways | PDF (3,931 KB) - Modularity of MAP kinases allows deformation of their signalling pathways | Supplementary information

STAT3 inhibition of gluconeogenesis is downregulated by SirT1 - pp492 - 500

Yongzhan Nie, Derek M. Erion, Zhenglong Yuan, Marcelo Dietrich, Gerald I. Shulman, Tamas L. Horvath & Qian Gao

doi:10.1038/ncb1857

STAT3 inhibits glucose production by suppressing the expression of key gluconeogenic genes. In a novel nutrient sensing pathway, the fasting activated longevity protein SirT11 promotes gluconeogenesis by suppressing this inhibitory effect of STAT3.

First Paragraph - STAT3 inhibition of gluconeogenesis is downregulated by SirT1 | Full Text - STAT3 inhibition of gluconeogenesis is downregulated by SirT1 | PDF (2,861 KB) - STAT3 inhibition of gluconeogenesis is downregulated by SirT1 | Supplementary information

Absence of nucleolar disruption after impairment of 40S ribosome biogenesis reveals an rpL11-translation-dependent mechanism of p53 induction - pp501 - 508

Stefano Fumagalli, Alessandro Di Cara, Arti Neb-Gulati, Francois Natt, Sandy Schwemberger, Jonathan Hall, George F. Babcock, Rosa Bernardi, Pier Paolo Pandolfi & George Thomas

doi:10.1038/ncb1858

Depletion of ribosomal protein S6 leads to upregulation of p53 and cell cycle arrest. Surprisingly, p53 induction is not due to nucleolar disruption and Mdm2 inhibition, but rather the selective translation of a class of mRNAs including ribosomal protein L11.

First Paragraph - Absence of nucleolar disruption after impairment of 40S ribosome biogenesis reveals an rpL11-translation-dependent mechanism of p53 induction | Full Text - Absence of nucleolar disruption after impairment of 40S ribosome biogenesis reveals an rpL11-translation-dependent mechanism of p53 induction | PDF (2,165 KB) - Absence of nucleolar disruption after impairment of 40S ribosome biogenesis reveals an rpL11-translation-dependent mechanism of p53 induction | Supplementary information

Electrochemical cues regulate assembly of the Frizzled/Dishevelled complex at the plasma membrane during planar epithelial polarization - p508

Matias Simons, William J. Gault, Daniel Gotthardt, Rajeev Rohatgi, Thomas J. Klein, Youming Shao, Ho-Jin Lee, Ai-Luen Wu, Yimin Fang, Lisa M. Satlin, Julian T. Dow, Jie Chen, Jie Zheng, Michael Boutros & Marek Mlodzik

doi:10.1038/ncb0409-508

Full Text - Electrochemical cues regulate assembly of the Frizzled/Dishevelled complex at the plasma membrane during planar epithelial polarization | PDF (184 KB) - Electrochemical cues regulate assembly of the Frizzled/Dishevelled complex at the plasma membrane during planar epithelial polarization