Volume 11 Issue 5, May 2009

A collection of seven reviews surveys how microorganisms subvert host cell biology.

Correct timing of developmental events is crucial for generating a normal organism. During oogenesis in Drosophila melanogaster, migration of border cells occurs in a defined temporal window and requires Jak/Stat and steroid hormone signalling. The initiation of border-cell migration is now shown to be timed by Jak/Stat-mediated downregulation of the BTB domain transcriptional regulator Abrupt, which acts as a negative regulator of steroid hormone signalling.

Focal adhesion turnover is essential for cell migration. New results show that the talin head liberated from talin by calpain II cleavage has a key role in these events, and that its levels are tightly regulated by Smurf1-mediated ubiquitylation counteracted by Cdk5-mediated phosphorylation.

SCAI is a newly discovered protein that reduces cancer cell invasiveness. SCAI inhibits the MAL/SRF transcriptional activator complex that is downstream of Rho GTPase and actin, resulting in reduced expression of β₁-integrins and loss of invasive potential.

The actin severing factor cofilin is activated by the slingshot phosphatases. Phosphorylation of slingshot 1L by protein kinase D is found to block the association of slingshot 1L with actin, thereby inhibiting cofilin activation and directed cell migration.

SCAI is novel protein that inhibits the transcription factor MAL and represses the expression of β₁-integrin. Reduced SCAI levels also correlate with increased invasive cell migration.

How temporal signals from the steroid hormone ecdysone are integrated with JAK/STAT-mediated spatial control of Drosophila border-cell migration has been unclear. JAK/STAT represses Abrupt, which in turn attenuates ecdysone signalling by interacting with the ecdysone receptor coactivator Taiman.

The tumour suppressor p53 can mediate both cell-cycle arrest and apoptosis. Apak binds and acetylates p53 by recruiting KAP-1 and HDAC1 to specifically suppress p53 regulated pro-apoptotic genes. Stress-induced phosphorylation of Apak by ATM relieves this inhibition.

The ubquitin ligase Rad18 is a central mediator of cell cycle checkpoint activation by DNA damage. Now Rad18 turns out to directly regulate homologous recombination repair by interacting with Rad51C

The 'somatic growth axis' involving IGF-1 and growth hormone is implicated in longevity. Persistent transcription-blocking DNA damage attenuates growth hormone and IGF-1 receptor expression and precipitates other ageing associated transcriptional changes, as well as inhibiting somatic growth.

Telomerase-negative cells maintain their telomeres through an alternative pathway that involves DNA recombination after replication. In this pathway, the recombination endonuclease MUS81 is found to regulate telomeric recombination and maintains the length of telomeres by interacting with the telomere binding protein TRF2.

Talins are essential for integrin activation, focal adhesion formation and mesenchymal cell migration. The E3 ubiquitin ligase Smurf1 regulates talin head degradation and Cdk5-mediated phosphorylation of the head prevents Smurf1 action on talin.

It has been controversial whether female germline stem cells (FGSCs) are present in postnatal mammalian ovaries. Cells from a line derived from FGSCs isolated from adult mice that were transplanted into ovaries of infertile animals underwent oogenesis and generated offspring.

Bone morphogenetic proteins (BMPs) regulate zebrafish dorsoventral patterning through two distinct receptor complexes. Surprisingly, BMPs function as an obligate heterodimer of BMP-2 and -7, while BMP homodimers are inactive.

Mitotic exit occurs when Cdc2 kinase activity drops and its substrates are dephosphorylated. Protein phosphatase-1 is responsible for this dephosphorylation and its activity is restrained during mitosis by Cdc2 phosphorylation and binding of Inhibitor-1, while auto-dephoshorylation at the Cdc2 site ensures its timely activation.

NF-κB activity is positively regulated through phosphorylation, but how activation is reversed has been unclear. A genome-wide siRNA screen reveals that the phosphatase WIP1 dephosphorylates the NF-κB subunit p65 at Ser 536, a phospho-residue critical for transcriptional regulation.

Nature Cell BiologyandNature Reviews Microbiologypresent a set of specially commissioned articles that highlight recent progress in our understanding of how microorganisms exploit the cell biology of their host.