Table of contents


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Editorial

An integrative future pE109

doi:10.1038/ncb0502-e109


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Letters to Editor

Chronic granulomatous disease mutations and the PX domain pE110

Paul G. Heyworth & Andrew R. Cross

doi:10.1038/ncb0502-e110a


Amyloid-lowering isocoumarins are not direct inhibitors of bold gamma-secretase ppE110 - E111

William P. Esler, Chittaranjan Das, William A. Campbell, W. Taylor Kimberly, Anna Y. Kornilova, Thekla S. Diehl, Wenjuan Ye, Beth L. Ostaszewski, Weiming Xia, Dennis J. Selkoe & Michael S. Wolfe

doi:10.1038/ncb0502-e110b


Amyloid-lowering isocoumarins are not direct inhibitors of bold gamma-secretase - Reponse ppE111 - E112

Agnes Petit, Cécile Dumanchin-Njock, David Andrau, Cristine Alves da Costa & Frédéric Checler

doi:10.1038/ncb0502-e110c


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Commentary

Taking a bite: proteasomal protein processing ppE113 - E116

Michael Rape & Stefan Jentsch

doi:10.1038/ncb0502-e113

The proteasome is a hollow cylindrical protease that contains active sites concealed within its central cavity. Proteasomes usually completely degrade substrates into small peptides, but in a few cases, degradation can yield biologically active protein fragments. Examples of this are the transcription factors NF-kappaB, Spt23p and Mga2p, which are generated from precursors by proteasomal processing. How distinct protein domains are spared from degradation remains a matter of debate. Here, we discuss several models and suggest a novel mechanism for proteasomal processing.


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News and Views

Cell polarity: Oskar seeks PARtner for a stable relationship ppE117 - E118

Simon L. Bullock & David Ish-Horowicz

doi:10.1038/ncb0502-e117

The Par-1/MARK kinases have a conserved role in cell polarization and are required to establish the anterior–posterior axis of Caenorhabditis elegans and Drosophila melanogaster. Now, elegant studies in Drosophila uncover the posterior patterning molecule Oskar (Osk) as a direct target of Par-1. Phosphorylation of Oskar at the posterior pole stabilizes the protein and contributes to its localized accumulation at high levels.

See also: Article by Riechmann et al.


Conspiracy to disarm APC in interphase ppE119 - E120

Hartmut C. Vodermaier & Jan-Michael Peters

doi:10.1038/ncb0502-e119

The anaphase-promoting complex (APC) initiates exit from mitosis by ubiquitinating A- and B-type cyclins, the activating subunits of cyclin-dependent kinase 1 (Cdk1). Subsequently, the APC has to be inactivated to allow the re-accumulation of mitotic cyclins in the next cell cycle. A newly identified inhibitor of the APC, called Emi1 in vertebrates and Rca1 in Drosophila melanogaster, may have an important function in inactivating the APC during interphase.

See also: Article by Hsu et al.


Ubiquitin chained and crosslinked ppE121 - E123

Daniel Finley

doi:10.1038/ncb0502-e121

Polyubiquitin chains are assembled onto proteins destined for degradation. The target protein is then unfolded by the proteasome and translocated through a channel leading from the unfolding site to an internal chamber of the enzyme for hydrolysis. A recent paper illuminates the long-elusive polyubiquitin chain recognition step that initiates this sequence of events at the proteasome.


An encore for kiss and run? pE123

Barbara Marte

doi:10.1038/ncb0502-e123


Getting legless with a Pygopus pE124

Sarah Greaves

doi:10.1038/ncb0502-e124

See also: Article by Thompson et al.


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Book Reviews

The forgotten chaperones pE125

Eric Solary & Carmen Garrido review Small Stress Proteins by A. P. Arrigo & W. E. G. Müller

doi:10.1038/ncb0502-e125


The role of cytometry in research and patient care pE126

Rafael Nunez reviews Cytometric analysis of cell phenotype and function by D. A. McCarthy & M. G. Macey

doi:10.1038/ncb0502-e126


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Historical Perspective

The origins of protein phosphorylation ppE127 - E130

Philip Cohen

doi:10.1038/ncb0502-e127


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Review

AP-1 as a regulator of cell life and death ppE131 - E136

Eitan Shaulian & Michael Karin

doi:10.1038/ncb0502-e131


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Articles

The TRPM7 channel is inactivated by PIP2 hydrolysis pp329 - 336

Loren W. Runnels, Lixia Yue & David E. Clapham

doi:10.1038/ncb781


Par-1 regulates stability of the posterior determinant Oskar by phosphorylation pp337 - 342

Veit Riechmann, Gustavo J. Gutierrez, Paolo Filardo, Angel R. Nebreda & Anne Ephrussi

doi:10.1038/ncb782

See also: News and Views by Bullock & Ish-Horowicz


Ras signalling on the endoplasmic reticulum and the Golgi pp343 - 350

Vi K. Chiu, Trever Bivona, Angela Hach, J. Bernard Sajous, Joseph Silletti, Heidi Wiener, Ronald L. Johnson, II, Adrienne D. Cox & Mark R. Philips

doi:10.1038/ncb783


Frodo interacts with Dishevelled to transduce Wnt signals pp351 - 357

Joachim Gloy, Hiroki Hikasa & Sergei Y. Sokol

doi:10.1038/ncb784


E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APCCdh1 pp358 - 366

Jerry Y. Hsu, Julie D.R. Reimann, Claus S. Sørensen, Jiri Lukas & Peter K. Jackson

doi:10.1038/ncb785

See also: News and Views by Vodermaier & Peters


A new nuclear component of the Wnt signalling pathway pp367 - 373

Barry Thompson, Fiona Townsley, Rina Rosin-Arbesfeld, Hannah Musisi & Mariann Bienz

doi:10.1038/ncb786

See also: News and Views by Greaves


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Brief Communications


Dysfunction of store-operated calcium channel in muscle cells lacking mg29 pp379 - 383

Zui Pan, Dongmei Yang, Ramakrishnan Y. Nagaraj, Thomas A. Nosek, Miyuki Nishi, Hiroshi Takeshima, Heping Cheng & Jianjie Ma

doi:10.1038/ncb788


Maintenance of replication forks and the S-phase checkpoint by Cdc18p and Orp1p pp384 - 388

Hiroshi Murakami, Stephanie K. Yanow, Dominic Griffiths, Makoto Nakanishi & Paul Nurse

doi:10.1038/ncb789


Epsins and Vps27p/Hrs contain ubiquitin-binding domains that function in receptor endocytosis pp389 - 393

Susan C. Shih, David J. Katzmann, Joshua D. Schnell, Myra Sutanto, Scott D. Emr & Linda Hicke

doi:10.1038/ncb790


Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes pp394 - 398

Camilla Raiborg, Kristi G. Bache, David J. Gillooly, Inger Helene Madshus, Espen Stang & Harald Stenmark

doi:10.1038/ncb791


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Erratum

Erratum p398

doi:10.1038/ncb792


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