News & Views in 2000

Recent studies have shown that under conditions of Golgi breakdown, Golgi glycosylation enzymes recycle to the endoplasmic reticulum (ER), whereas Golgi matrix proteins are retained in a set of cytoplasmic membranes. These findings have implications for the role of the ER in Golgi reassembly.

ATM, the product of the gene that is mutated in the human genetic disorder ataxia telangiectasia (A-T), responds to DNA damage by phosphorylating several key substrates that are involved in both the sensing of damage and the activation of cell-cycle checkpoints. The unexpected activation of ATM kinase in response to insulin supports a more general signalling role for this enzyme.

Moving proteins between cellular locations is proving to be a tightly regulated process, and provides an important mechanism for controlling protein function. The tumour-suppressor protein p53 has been shown to use microtubules to aid nuclear localization, a finding that raises interesting questions about the action of microtubule-disrupting chemotherapeutic drugs.

The catenin p120 protein functions as a traffic light at the crossroads between cell–cell adhesion and cell migration. It can influence the choice between sessile and migratory behaviour by interfering with the function of RHO proteins.

Regulated ubiquitin/proteasome-dependent processing controls transcription by triggering the release of dormant transcriptional activators from the endoplasmic reticulum. This intersection of transcription and proteolysis has important implications for gene control, proteasome–substrate interactions and signal integration.

Combined efforts of developmental biologists and cancer geneticists have outlined the canonical Wnt/Wingless (Wg) signalling pathway as we currently know it. At the heart of the pathway is the molecule β-catenin/Armadillo. Recent work has shown that the tumour suppressor adenomatous polyposis coli (APC) acts to shuttle β-catenin from the nucleus to the cytoplasm.

Protein kinases play an integral role in the regulation of virtually every major cellular and developmental process, and an understanding of how protein kinases function in vivo is therefore of central importance to cell biology. Newly developed protein-kinase inhibitors provide powerful tools for understanding the functions of kinases in vivo.

Acetylcholine calms the heartbeat by activating G_i-coupled receptors and G-protein-activated inwardly rectifying potassium (GIRK) channels. It also dampens the GIRK current by reducing PIP₂ through G_q-coupled receptors. These two types of receptors seem to be engaged in an intriguingly specific form of crosstalk, which leads to desensitization of the GIRK current.

Although it has long been appreciated that cAMP-related signalling can control cell growth, the mechanism by which this control is exerted has remained unknown. However, new findings now show how cAMP, acting through protein kinase A (PKA), maintains cells in an anchorage-dependent state by inhibiting mitogen-activated protein kinase (MAPK) signalling through p21-activated kinases (PAKs).

Covalent modification of the oncogene product Mdm2 by the ubiquitin-related protein SUMO1 protects it from ubiquitination and enhances its E3 ligase activity towards p53 in vitro. Disappearance of SUMO-modified Mdm2, which is observed upon radiation, may thus be a prerequisite for DNA-damage-induced accumulation of p53.

The molecular pathways that mediate apoptosis are tightly regulated by a series of positive and negative signals, the balance of which determines whether or not cells commit suicide. New data from several laboratories now show that heat-shock proteins (HSPs) can influence this process through direct physical interaction with key components of the apoptotic machinery. These reports marry the survival (or death)-endowing properties of HSPs to the cell-death pathway.