2010 Vol. 1, No. 9

News and views
Importin-β2: a key to two gates?
Kaiyao Huang, Che-Chia Tsao
2010, 1(9): 791-792. doi: 10.1007/s13238-010-0103-1
Father of biological cloning in China
Zuoyan Zhu, Ming Li, Le Kang
2010, 1(9): 793-794. doi: 10.1007/s13238-010-0106-y
Apoptotic regulation and tRNA
Yide Mei, Aaron Stonestrom, Ya-Ming Hou, Xiaolu Yang
2010, 1(9): 795-801. doi: 10.1007/s13238-010-0107-x
Apoptotic regulation is critical to organismal homeostasis and protection against many human disease processes such as cancer. Significant research efforts over the past several decades have illuminated many signaling molecules and effecter proteins responsible for this form of programmed cell death. Recent evidence suggests that transfer RNA (tRNA) regulates apoptotic sensitivity at the level of cytochrome c-mediated apoptosome formation. This finding unexpectedly places tRNA at the nexus of cellular biosynthesis and survival. Here we review the current understanding of both the apoptotic machinery and tRNA biology. We describe the evidence linking tRNA and cytochrome c in depth, and speculate on the implications of this link in cell biology.
Heteromerization of TRP channel subunits: extending functional diversity
Wei Cheng, Changsen Sun, Jie Zheng
2010, 1(9): 802-810. doi: 10.1007/s13238-010-0108-9
Transient receptor potential (TRP) channels are widely found throughout the animal kingdom. By serving as cellular sensors for a wide spectrum of physical and chemical stimuli, they play crucial physiological roles ranging from sensory transduction to cell cycle modulation. TRP channels are tetrameric protein complexes. While most TRP subunits can form functional homomeric channels, heteromerization of TRP channel subunits of either the same subfamily or different subfamilies has been widely observed. Heteromeric TRP channels exhibit many novel properties compared to their homomeric counterparts, indicating that co-assembly of TRP channel subunits has an important contribution to the diversity of TRP channel functions.
Snapshots of a hybrid transcription factor in the Hippo pathway
Xuelian Luo
2010, 1(9): 811-819. doi: 10.1007/s13238-010-0105-z
The Hippo pathway plays key roles in animal development. It suppresses tumorigenesis by controlling the transcription of the target genes that are critical for cell proliferation and apoptosis. The transcriptional coactivator YAP is the major downstream effector of the Hippo signaling. Upon extracellular stimulation, a kinase cascade in the Hippo pathway phosphorylates YAP and promotes its cytoplasmic sequestration by 14-3-3 and ubiquitin-dependent degradation. When the Hippo pathway is turned off, YAP (which lacks a DNA-binding domain) is dephosphorylated and translocates to the nucleus, where it associates with the transcription factor TEAD to form a functional heterodimeric transcription factor and to promote the expression of the Hipporesponsive genes. Recently, structures of the YAPbinding domain of TEAD alone or in complex with YAP have revealed the atomic details of the TEAD-YAP interaction. Here, I review these exciting advances, propose a strategy for targeting the TEAD-YAP interaction using small molecules, and suggest potential mechanisms by which phosphorylation and 14-3-3 binding regulate the cytoplasmic retention of YAP.
Nucleosome assembly and epigenetic inheritance
Mo Xu, Bing Zhu
2010, 1(9): 820-829. doi: 10.1007/s13238-010-0104-0
In eukaryotic cells, histones are packaged into octameric core particles with DNA wrapping around to form nucleosomes, which are the basic units of chromatin (Kornberg and Thomas, 1974). Multicellular organisms utilise chromatin marks to translate one single genome into hundreds of epigenomes for their corresponding cell types. Inheritance of epigenetic status is critical for the maintenance of gene expression profile during mitotic cell divisions (Allis et al., 2006). During S phase, canonical histones are deposited onto DNA in a replication-coupled manner (Allis et al., 2006). To understand how dividing cells overcome the dilution of epigenetic marks after chromatin duplication, DNA replication coupled (RC) nucleosome assembly has been of great interest. In this review, we focus on the potential influence of RC nucleosome assembly processes on the maintenance of epigenetic status.
Melanization in living organisms: a perspective of species evolution
Christopher J Vavricka, Bruce M. Christensen, Jianyong Li
2010, 1(9): 830-841. doi: 10.1007/s13238-010-0109-8
Eumelanin is a heteropolymer that is generally composed of hydroxylated indole residues and plays diverse protective functions in various species. Melanin is derived from the amino acid tyrosine and production of melanin is a highly complex oxidative process with a number of steps that can either proceed enzymatically or non-enzymatically. Although melanin plays important protective roles in many species, during melanization, particularly in steps that can proceed non-enzymatically, many toxic intermediates are produced, including semiquinones, dopaquinone, indole-quinones and moreover, the production of many reactive oxygen species. To mitigate the production of reactive species, a number of proteins that regulate the biochemical process of melanization have evolved in various living species, which is closely related to adaptation and physiological requirements. In this communication, we discuss differences between non-enzymatic and enzymatic processes of melanization and the enzymatic regulation of melanization in difference species with an emphasis on differences between mammals and insects. Comparison between melanization and insect sclerotization is also emphasized which raises some interesting questions about the current models of these pathways.
Aptamer-based and DNAzyme-linked colorimetric detection of cancer cells
Xiaoli Zhu, Ya Cao, Zhiqiang Liang, Genxi Li
2010, 1(9): 842-846. doi: 10.1007/s13238-010-0110-2
This paper reports a novel method to detect human leukemic lymphoblasts (CCRF-CEM cells). While the aptamer of the cancer cells was employed as the recognition element to target cancer cells, peroxidaseactive DNAzyme was used as the sensing element to produce catalysis-induced colorimetric signals. The elegant architecture integrating the aptamer and DNAzyme made it feasible to detect cancer cells easily and rapidly by the color change of the substrate for DNAzyme. Experimental results showed that 500 cells can well indicate the cancer, while as control, 250,000 Islet Island Beta cells only show tiny signals, suggesting that the method proposed in this paper has considerable sensitivity and selectivity. Furthermore, since it does not require expensive apparatus, or modification or label of DNA chains, the method we present here is also costeffective and conveniently operated, implying potential applications in future cancer diagnosis.
Research articles
Nucleotide bias of DCL and AGO in plant anti-virus gene silencing
Thien Ho, Liang Wang, Linfeng Huang, Zhigang Li, Denise W. Pallett, Tamas Dalmay, Kazusato Ohshima, John A. Walsh, Hui Wang
2010, 1(9): 847-858. doi: 10.1007/s13238-010-0100-4
Plant Dicer-like (DCL) and Argonaute (AGO) are the key enzymes involved in anti-virus post-transcriptional gene silencing (AV-PTGS). Here we show that AV-PTGS exhibited nucleotide preference by calculating a relative AV-PTGS efficiency on processing viral RNA substrates. In comparison with genome sequences of dicot-infecting Turnip mosaic virus (TuMV) and monocot-infecting Cocksfoot streak virus (CSV), viral-derived small interfering RNAs (vsiRNAs) displayed positive correlations between AV-PTGS efficiency and G + C content (GC%). Further investigations on nucleotide contents revealed that the vsiRNA populations had G-biases. This finding was further supported by our analyses of previously reported vsiRNA populations in diverse plant-virus associations, and AGO associated Arabidopsis endogenous siRNA populations, indicating that plant AGOs operated with G-preference. We further propose a hypothesis that AV-PTGS imposes selection pressure(s) on the evolution of plant viruses. This hypothesis was supported when potyvirus genomes were analysed for evidence of GC elimination, suggesting that plant virus evolution to have low GC% genomes would have a unique function, which is to reduce the host AV-PTGS attack during infections.
Identification of four novel DC-SIGN ligands on Mycobacterium bovis BCG
Maria V. Carroll, Robert B. Sim, Fabiana Bigi, Anne Jäkel, Robin Antrobus, Daniel A. Mitchell
2010, 1(9): 859-870. doi: 10.1007/s13238-010-0101-3
Dendritic-cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN; CD209) has an important role in mediating adherence of Mycobacteria species, including M. tuberculosis and M. bovis BCG to human dendritic cells and macrophages, in which these bacteria can survive intracellularly. DC-SIGN is a C-type lectin, and interactions with mycobacterial cells are believed to occur via mannosylated structures on the mycobacterial surface. Recent studies suggest more varied modes of binding to multiple mycobacterial ligands. Here we identify, by affinity chromatography and mass-spectrometry, four novel ligands of M. bovis BCG that bind to DC-SIGN. The novel ligands are chaperone protein DnaK, 60 kDa chaperonin-1 (Cpn60.1), glyceraldehyde-3 phosphate dehydrogenase (GAPDH) and lipoprotein lprG. Other published work strongly suggests that these are on the cell surface. Of these ligands, lprG appears to bind DC-SIGN via typical proteinglycan interactions, but DnaK and Cpn60.1 binding do not show evidence of carbohydrate-dependent interactions. LprG was also identified as a ligand for DC-SIGNR (L-SIGN; CD299) and the M. tuberculosis orthologue of lprG has been found previously to interact with human toll-like receptor 2. Collectively, these findings offer new targets for combating mycobacterial adhesion and within-host survival, and reinforce the role of DCSIGN as an important host ligand in mycobacterial infection.
Regulation of the protein stability of POSH and MLK family
Chunyan Wang, Yang Tao, Yaqing Wang, Zhiheng Xu
2010, 1(9): 871-878. doi: 10.1007/s13238-010-0111-1
Sequential activation of the JNK pathway components, including Rac1/Cdc42, MLKs (mixed-lineage kinases), MKK4/7 and JNKs, plays a required role in many cell death paradigms. Those components are organized by a scaffold protein, POSH (Plenty of SH3's), to ensure the effective activation of the JNK pathway and cell death upon apoptotic stimuli. We have shown recently that the expression of POSH and MLK family proteins are regulated through protein stability. By generating a variety of mutants, we provide evidence here that the Nterminal half of POSH is accountable for its stability regulation and its over-expression-induced cell death. In addition, POSH's ability to induce apoptosis is correlated with its stability as well as its MLK binding ability. MLK family's stability, like that of POSH, requires activation of JNKs. However, we were surprised to find out that the widely used dominant negative (d/n) form of c-Jun could down-regulate MLK's stability, indicating that peptide from d/n c-Jun can be potentially developed into a therapeutical drug.