Hot off the presses! Nov 01 Nat Rev Mol Cell Biol

The Nov 01 issue of the Nat Rev Mol Cell Biol is now up on Pubget (About Nat Rev Mol Cell Biol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

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  - Nat Rev Mol Cell Biol 12(11):687 (2011)
  
• Ageing: A midlife crisis for sirtuins | PDF (460 KB)
  - Nat Rev Mol Cell Biol 12(11):688 (2011)
  Sirtuins are NAD+-dependent protein deacetylases that are believed to promote longevity in several organisms. Although controversial, the connection between sirtuins and extended lifespan has dramatically boosted research into these proteins over the past 10 years; but now this link is being challenged again.
• Deconstructing the cell cycle | PDF (110 KB)
  - Nat Rev Mol Cell Biol 12(11):689 (2011)
  When I was an undergraduate student, knowing three key concepts would ensure success in 'Cell Cycle 101': that oscillations of cyclin–cyclin dependent kinase (CDK) complexes drive the cell cycle; that directionality is ensured by the irreversibility of periodic proteasome-mediated cyclin degradation; and that checkpoints ensure the dependence of later cell cycle steps on the completion of earlier events. A recent study by Coudreuse and Nurse now suggests that only the first concept may be fundamentally essential for cell cycle progression.
• Cell signalling: PRMT5 restricts ERK activity | PDF (279 KB)
  - Nat Rev Mol Cell Biol 12(11):689 (2011)
  Growth factors can activate the RAS–RAF–MEK–ERK (RAS–RAF–MAPK/ERK kinase (also known as MAPKK)–extracellular signal-regulated kinase) pathway with different kinetics to result in distinct biological outcomes. For example, ERK activation in PC12 cells is high and sustained in response to nerve growth factor (NGF), resulting in cell differentiation, but low and transient in response to epidermal growth factor (EGF), resulting in cell proliferation.
• DNA repair: Nuclear receptors in repair | PDF (187 KB)
  - Nat Rev Mol Cell Biol 12(11):690 (2011)
  Nuclear receptor subfamily 4 group A (NR4A) orphan nuclear receptors are thought to act as ligand-independent transcription factors that mediate adaptive and stress responses. Their loss has also been linked to an accumulation of DNA damage, but this was considered to be an indirect effect of altered transcription.
• Organelle dynamics: Inheritance for pluripotency | PDF (429 KB)
  - Nat Rev Mol Cell Biol 12(11):690 (2011)
  Midbodies — which form during cytokinesis in the intercellular bridge between two daughter cells and are required for their separation — can remain in daughter cells as midbody derivatives (MBds), the fate and function of which are unclear. Kuo, Chen and colleagues.
• Mechanisms of disease: USP1 keeps ID proteins stable | PDF (266 KB)
  - Nat Rev Mol Cell Biol 12(11):691 (2011)
  Basic helix–loop–helix transcription factors, which are regulators of development and differentiation, are inhibited by the DNA-binding protein inhibitors ID1, ID2, ID3 and ID4. ID proteins are abundant in embryonic and adult stem cells, and are overexpressed in some dedifferentiated primary tumours, suggesting that they might help to maintain stem cell fate.
• Chromatin: Chromatin state reaches out | PDF (143 KB)
  - Nat Rev Mol Cell Biol 12(11):692 (2011)
  Histone modifications have many effects on chromatin organization and gene regulation, and studies have shown that modification of one residue may affect that of another, either in cis (on the same histone) or in trans (on another histone). Latham et al.
• Stem cells: The 'backup' intestinal stem cell | PDF (141 KB)
  - Nat Rev Mol Cell Biol 12(11):692 (2011)
  Two stem cell populations have been identified in the small intestine epithelium: fast-cycling stem cells termed crypt base columnar cells (CBCs), which express Leu-rich repeat-containing GPCR 5 (LGR5) and are ubiquitous; and slower-cycling stem cells, which express the polycomb protein BMI1 and are rarer. de Sauvage, Klein and colleagues investigated the functions and relationship of the two populations and found that BMI1-expressing cells can repopulate the epithelium of the small intestine in the absence of LGR5-expressing CBCs.
• Reprogramming revitalized | PDF (74 KB)
  - Nat Rev Mol Cell Biol 12(11):692 (2011)
  Somatic cell nuclear transfer has been used successfully for the first time to generate human pluripotent stem cells.
• Cell polarity: PAR access control | PDF (97 KB)
  - Nat Rev Mol Cell Biol 12(11):693 (2011)
  The Caenorhabditis elegans zygote rapidly establishes regional domains of partitioning defective (PAR) polarity factors along the anterior–posterior axis. Microtubules can affect this, and Seydoux and colleagues now show that this is through microtubule-mediated local protection of PAR-2.
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  - Nat Rev Mol Cell Biol 12(11):693 (2011)
  
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  - Nat Rev Mol Cell Biol 12(11):693 (2011)
  
• The nucleoskeleton as a genome-associated dynamic 'network of networks'
  - Nat Rev Mol Cell Biol 12(11):695 (2011)
  In the cytosol, actin polymers, intermediate filaments and microtubules can anchor to cell surface adhesions and interlink to form intricate networks. This cytoskeleton is anchored to the nucleus through LINC (links the nucleoskeleton and cytoskeleton) complexes that span the nuclear envelope and in turn anchor to networks of filaments in the nucleus. The metazoan nucleoskeleton includes nuclear pore-linked filaments, A-type and B-type lamin intermediate filaments, nuclear mitotic apparatus (NuMA) networks, spectrins, titin, 'unconventional' polymers of actin and at least ten different myosin and kinesin motors. These elements constitute a poorly understood 'network of networks' that dynamically reorganizes during mitosis and is responsible for genome organization and integrity.
• Microtubule nucleation by γ-tubulin complexes
  - Nat Rev Mol Cell Biol 12(11):709 (2011)
  Microtubule nucleation is regulated by the γ-tubulin ring complex (γTuRC) and related γ-tubulin complexes, providing spatial and temporal control over the initiation of microtubule growth. Recent structural work has shed light on the mechanism of γTuRC-based microtubule nucleation, confirming the long-standing hypothesis that the γTuRC functions as a microtubule template. The first crystallographic analysis of a non-γ-tubulin γTuRC component (γ-tubulin complex protein 4 (GCP4)) has resulted in a new appreciation of the relationships among all γTuRC proteins, leading to a refined model of their organization and function. The structures have also suggested an unexpected mechanism for regulating γTuRC activity via conformational modulation of the complex component GCP3. New experiments on γTuRC localization extend these insights, suggesting a direct link between its attachment at specific cellular sites and its activation.
• Forming functional fat: a growing understanding of adipocyte differentiation
  - Nat Rev Mol Cell Biol 12(11):722 (2011)
  Adipose tissue, which is primarily composed of adipocytes, is crucial for maintaining energy and metabolic homeostasis. Adipogenesis is thought to occur in two stages: commitment of mesenchymal stem cells to a preadipocyte fate and terminal differentiation. Cell shape and extracellular matrix remodelling have recently been found to regulate preadipocyte commitment and competency by modulating WNT and RHO-family GTPase signalling cascades. Adipogenic stimuli induce terminal differentiation in committed preadipocytes through the epigenomic activation of peroxisome proliferator-activated receptor-γ (PPARγ). The coordination of PPARγ with CCAAT/enhancer-binding protein (C/EBP) transcription factors maintains adipocyte gene expression. Improving our understanding of these mechanisms may allow us to identify therapeutic targets against metabolic diseases that are rapidly becoming epidemic globally.
• The N-end rule pathway: emerging functions and molecular principles of substrate recognition
  - Nat Rev Mol Cell Biol 12(11):735 (2011)
  The N-end rule defines the protein-destabilizing activity of a given amino-terminal residue and its post-translational modification. Since its discovery 25 years ago, the pathway involved in the N-end rule has been thought to target only a limited set of specific substrates of the ubiquitin–proteasome system. Recent studies have provided insights into the components, substrates, functions and structural basis of substrate recognition. The N-end rule pathway is now emerging as a major cellular proteolytic system, in which the majority of proteins are born with or acquire specific N-terminal degradation determinants through protein-specific or global post-translational modifications.
• Imaging the coordination of multiple signalling activities in living cells
  - Nat Rev Mol Cell Biol 12(11):749 (2011)
  Cellular signal transduction occurs in complex and redundant interaction networks, which are best understood by simultaneously monitoring the activation dynamics of multiple components. Recent advances in biosensor technology have made it possible to visualize and quantify the activation of multiple network nodes in the same living cell. The precision and scope of this approach has been greatly extended by novel computational approaches (referred to as computational multiplexing) that can reveal relationships between network nodes imaged in separate cells.
• It cuts both ways: reconciling the dual roles of caspase 8 in cell death and survival
  - Nat Rev Mol Cell Biol 12(11):757 (2011)
  Caspase 8 can initiate apoptosis, but it also has non-apoptotic roles; for example, it is required for embryonic development and immune cell proliferation. Recent work has indicated that the requirement for caspase 8 in development and immune cell proliferation is defined by suppression of receptor-interacting protein kinase 3 (RIPK3), a kinase that triggers an alternative form of cell death called programmed necrosis. Interestingly, these recent findings can be reconciled with earlier work on the non-apoptotic roles of caspase 8.