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

The Oct 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:

• From the editors
  - Nat Rev Mol Cell Biol 10(10):651 (2009)
  
• Small RNAS: Keeping let-7 young
  - Nat Rev Mol Cell Biol 10(10):652 (2009)
  
• Cell signalling: Free ubiquitin!
  - Nat Rev Mol Cell Biol 10(10):653 (2009)
  
• The matrix revolutions
  - Nat Rev Mol Cell Biol 10(10):653 (2009)
  
• Technology: GTPase activation at the leading edge
  - Nat Rev Mol Cell Biol 10(10):654 (2009)
  
• DNA replication: Unwinding maxicircle DNA
  - Nat Rev Mol Cell Biol 10(10):654 (2009)
  
• Systems biology: Cell biology put in context
  - Nat Rev Mol Cell Biol 10(10):655 (2009)
  
• Chromatin: A variant function for H2AZ
  - Nat Rev Mol Cell Biol 10(10):656 (2009)
  
• Small RNAs: RISCs hitch a ride
  - Nat Rev Mol Cell Biol 10(10):656 (2009)
  
• In brief: Cell death, Cell death, Cytoskeleton
  - Nat Rev Mol Cell Biol 10(10):656 (2009)
  
• Reconstructed egg for IVF
  - Nat Rev Mol Cell Biol 10(10):657 (2009)
  
• Ubiquitin-binding domains — from structures to functions
  - Nat Rev Mol Cell Biol 10(10):659-671 (2009)
  Ubiquitin-binding domains (UBDs) are modular elements that bind non-covalently to the protein modifier ubiquitin. Recent atomic-level resolution structures of ubiquitin–UBD complexes have revealed some of the mechanisms that underlie the versatile functions of ubiquitin in vivo. The preferences of UBDs for ubiquitin chains of specific length and linkage are central to these functions. These preferences originate from multimeric interactions, whereby UBDs synergistically bind multiple ubiquitin molecules, and from contacts with regions that link ubiquitin molecules into a polymer. The sequence context of UBDs and the conformational changes that follow their binding to ubiquitin also contribute to ubiquitin signalling. These new structure-based insights provide strategies for controlling cellular processes by targeting ubiquitin–UBD interfaces.
• Systems biology of stem cell fate and cellular reprogramming
  Macarthur BD Ma'ayan A Lemischka IR - Nat Rev Mol Cell Biol 10(10):672-681 (2009)
  Stem cell differentiation and the maintenance of self-renewal are intrinsically complex processes requiring the coordinated dynamic expression of hundreds of genes and proteins in precise response to external signalling cues. Numerous recent reports have used both experimental and computational techniques to dissect this complexity. These reports suggest that the control of cell fate has both deterministic and stochastic elements: complex underlying regulatory networks define stable molecular 'attractor' states towards which individual cells are drawn over time, whereas stochastic fluctuations in gene and protein expression levels drive transitions between coexisting attractors, ensuring robustness at the population level.
• Kinesin superfamily motor proteins and intracellular transport
  - Nat Rev Mol Cell Biol 10(10):682-696 (2009)
  Intracellular transport is fundamental for cellular function, survival and morphogenesis. Kinesin superfamily proteins (also known as KIFs) are important molecular motors that directionally transport various cargos, including membranous organelles, protein complexes and mRNAs. The mechanisms by which different kinesins recognize and bind to specific cargos, as well as how kinesins unload cargo and determine the direction of transport, have now been identified. Furthermore, recent molecular genetic experiments have uncovered important and unexpected roles for kinesins in the regulation of such physiological processes as higher brain function, tumour suppression and developmental patterning. These findings open exciting new areas of kinesin research.
• Mechanisms of Polycomb gene silencing: knowns and unknowns
  - Nat Rev Mol Cell Biol 10(10):697-708 (2009)
  Polycomb proteins form chromatin-modifying complexes that implement transcriptional silencing in higher eukaryotes. Hundreds of genes are silenced by Polycomb proteins, including dozens of genes that encode crucial developmental regulators in organisms ranging from plants to humans. Two main families of complexes, called Polycomb repressive complex 1 (PRC1) and PRC2, are targeted to repressed regions. Recent studies have advanced our understanding of these complexes, including their potential mechanisms of gene silencing, the roles of chromatin modifications, their means of delivery to target genes and the functional distinctions among variant complexes. Emerging concepts include the existence of a Polycomb barrier to transcription elongation and the involvement of non-coding RNAs in the targeting of Polycomb complexes. These findings have an impact on the epigenetic programming of gene expression in many biological systems.
• Structural and functional constraints in the evolution of protein families
  - Nat Rev Mol Cell Biol 10(10):709-720 (2009)
  High-throughput genomic sequencing has focused attention on understanding differences between species and between individuals. When this genetic variation affects protein sequences, the rate of amino acid substitution reflects both Darwinian selection for functionally advantageous mutations and selectively neutral evolution operating within the constraints of structure and function. During neutral evolution, whereby mutations accumulate by random drift, amino acid substitutions are constrained by factors such as the formation of intramolecular and intermolecular interactions and the accessibility to water or lipids surrounding the protein. These constraints arise from the need to conserve a specific architecture and to retain interactions that mediate functions in protein families and superfamilies.
• Protein denitrosylation: enzymatic mechanisms and cellular functions
  - Nat Rev Mol Cell Biol 10(10):721-732 (2009)
  S-Nitrosylation, the redox-based modification of Cys thiol side chains by nitric oxide, is a common mechanism in signal transduction. Dysregulated S-nitrosylation contributes to a range of human pathologies. New roles for protein denitrosylation in regulating S-nitrosylation are being revealed. Recently, several denitrosylases — the enzymes that mediate Cys denitrosylation — have been discovered, of which two enzyme systems in particular, the S-nitrosoglutathione reductase and thioredoxin systems, have been shown to be physiologically relevant. These highly conserved enzymes regulate signalling through multiple classes of receptors and influence diverse cellular responses. In addition, they protect from nitrosative stress in microorganisms, mammals and plants, thereby exerting profound effects on host–microbe interactions and innate immunity.