Band 4, Heft 2

Non-coding RNAs have emerged as key regulators in diverse cellular processes. Y RNAs are ∼100-nucleotide-long non-coding RNAs that show high conservation in metazoans. Human Y RNAs are known to bind to the Ro60 and La proteins to form the Ro ribonucleoprotein complex. Their main biological function appears to be in mediating the initiation of chromosomal DNA replication, regulating the autoimmune protein Ro60, and generating smaller RNA fragments following cellular stress, although the precise molecular mechanisms underlying these functions remain elusive. Here, we aim to review the most recent literature on Y RNAs and gain insight into the function of these intriguing molecules.

After its initial definition in 1999, the TCP family of transcription factors has become the focus of a multiplicity of studies related with plant development at the cellular, organ, and tissue levels. Evidence has accumulated indicating that TCP transcription factors are the main regulators of plant form and architecture and constitute a tool through which evolution shapes plant diversity. The TCP transcription factors act in a multiplicity of pathways related with cell proliferation and hormone responses. In recent years, the molecular pathways of TCP protein action and biochemical studies on their mode of interaction with DNA have begun to shed light on their mechanism of action. However, the available information is fragmented and a unifying view of TCP protein action is lacking, as well as detailed structural studies of the TCP-DNA complex. Also important, the possible role of TCP proteins as integrators of plant developmental responses to the environment has deserved little attention. In this review, we summarize the current knowledge about the structure and functions of TCP transcription factors and analyze future perspectives for the study of the role of these proteins and their use to modify plant development.

The Src family kinases Yes, Fyn, and c-Src play a pivotal role in regulating diverse liver functions such as bile flow, proteolysis, apoptosis, and proliferation and are regulated by anisoosmotic cell volume changes, death receptor ligands, and bile acids. For example, cell swelling leads to an integrin-sensed and focal adhesion kinase-mediated activation of c-Src-triggering choleresis, proteolysis inhibition, regulatory volume decrease via p38 MAPK and proliferation via the activation of the epidermal growth factor receptor and extracellular regulated kinases 1 and 2. In contrast, hepatocyte shrinkage generates an almost instantaneous oxidative stress response that triggers the activation of c-Jun N-terminal kinase and the Src family kinases Fyn and Yes. Whereas Fyn activation mediates cholestasis, Yes triggers CD95 activation and apoptosis. This review will discuss the role of Src family kinases in the regulation of liver function with emphasis on their role in osmo-signaling and bile acid signaling.

Metallothioneins (MTs) are a family of universal, small proteins, sharing a high cysteine content and an optimal capacity for metal ion coordination. They take part in a plethora of metal ion-related events (from detoxification to homeostasis, storage, and delivery), in a wide range of stress responses, and in different pathological processes (tumorigenesis, neurodegeneration, and inflammation). The information on both intracellular and extracellular interactions of MTs with other proteins is here comprehensively reviewed. In mammalian kidney, MT1/MT2 interact with megalin and related receptors, and with the transporter transthyretin. Most of the mammalian MT partners identified concern interactions with central nervous system (mainly brain) proteins, both through physical contact or metal exchange reactions. Physical interactions mainly involve neuronal secretion multimers. Regarding metal swap events, brain MT3 appears to control the metal ion load in peptides whose aggregation leads to neurodegenerative disorders, such as Aβ peptide, α-synuclein, and prion proteins (Alzheimer’s and Parkinson’s diseases, and spongiform encephalopathies, respectively). Interaction with ferritin and bovine serum albumin are also documented. The intercourse of MTs with zinc-dependent enzymes and transcription factors is capable to activate/deactivate them, thus conferring MTs the role of metabolic and gene expression regulators. As some of these proteins are involved in cell cycle and proliferation control (p53, nuclear factor κB, and PKCμ), they are considered in the context of oncogenesis and tumor progression. Only one non-mammalian MT interaction, involving Drosophila MtnA and MtnB major isoforms and peroxiredoxins, has been reported. The prospective use for biomedical applications of the MT-interaction information is finally discussed.

The inhibitors of apoptosis proteins (IAPs) are endogenous inhibitors for apoptosis. Apoptosis is carried out by caspases, which are the family of cystein proteases. IAPs regulate caspases through two conserved regions, the baculovirus IAP repeats (BIRs) and the really interesting new gene (RING) domains. Although the BIRs are responsible for binding to caspases, the RING domain can act as a ubiquitin-E3 ligase, leading to ubiquitylation of IAPs themselves and their pro-apoptotic IAP counterparts such as caspases. Recently, it is reported that another ubiquitin-like protein, neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8), is also involved in the regulation of apoptosis through neddylation of caspases mediated by IAPs. On the contrary, the results against the function of IAPs as a NEDD8-E3 ligase are also suggested. This review presents the summary of IAPs, caspases, and the ubiquitin-proteasome system and how their interactions influence the regulation of apoptosis.

The inability of adult cells to produce well-organized, robust elastic fibers has long been a barrier to the successful engineering of certain tissues. In this review, we focus primarily on elastin with respect to tissue-engineered vascular substitutes. To understand elastin regulation during normal development, we describe the role of various elastic fiber accessory proteins. Biochemical pathways regulating expression of the elastin gene are addressed, with particular focus on tissue-engineering research using adult-derived cells.

A wide variety of environmental cues, including inflammatory cytokines, ligands for pattern recognition receptors and endogenous danger signals, activate the inducible transcription factor nuclear factor-κB (NF-κB), which is a central regulator of inflammatory and immune responses. Excessive activation of NF-κB results in the development of severe diseases, such as chronic inflammatory disorders, autoimmune diseases and cancer. Therefore, the transcriptional activity of NF-κB is tightly regulated at multiple steps. One mechanism is mediated by the inhibitor of κB (IκB), a well-defined regulator of NF-κB that resides in the cytoplasm and prevents NF-κB from nuclear entry by sequestration. Recently, several atypical IκBs that reside in the nucleus were identified: Bcl-3, IκBζ, IκBNS and IκBη. In contrast to conventional IκBs, these atypical IκBs positively and negatively modulate NF-κB-mediated transcription. The function of atypical IκBs is independent of the prevention of NF-κB nuclear entry. Therefore, atypical IκBs are considered distinct from conventional IκBs and have been termed ‘nuclear IκBs.’ In addition to these members, our recent study indicated that IκBL, originally reported as a susceptibility gene for rheumatoid arthritis, also serves as a nuclear IκB. Biological and genetic studies strongly suggest that nuclear IκBs play important roles in the pathogenesis of inflammatory and autoimmune diseases via the regulation of both innate and adaptive immunity. In this review, we discuss the recent advances in our understanding of nuclear IκBs in the context of NF-κB-mediated transcriptional regulation and inflammatory responses.

Peroxisomes are ubiquitous organelles that enclose catalases, fatty acid-oxidizing enzymes, and a variety of proteins involved in different cellular processes. Interestingly, the late enzymes involved in penicillin biosynthesis, and the isopenicillin N epimerization enzymes involved in cephalosporin biosynthesis are located inside peroxisomes in the producer fungi Penicillium chrysogenum and Acremonium chrysogenum. Peroxisome proteins are targeted to those organelles by peroxisomal targeting signals located at the C-terminus (PTS1) or near the N-terminal end (PTS2) of those proteins. Peroxisomal membrane proteins (PMPs) are largely recruited by the interaction with specific sequences in the Pex19 protein. The compartmentalization into peroxisomes of several steps of the biosynthesis of penicillin, cephalosporin, and other secondary metabolites raises the question of how the precursors and/or intermediates of the biosynthesis of β-lactam antibiotics are transported into peroxisomes and the mechanisms of secretion of the final products (penicillin or cephalosporin) from peroxisomes to the extracellular medium. Recent advances in peroxisome proteomics, immunoelectron microscopy, and fluorescence labeling have shown that the transport of these intermediates is mediated by membrane proteins of the major facilitator superfamily class (drug/H + antiporters) containing 12 transmembrane-spanning domains (TMS). In some cases, the transport of the substrates (e.g., fatty acids) or intermediates may be mediated by ATP-binding cassette (ABC) transporters. Knowledge on the transport and secretion mechanisms is of paramount importance to understand the complex mechanisms of cell differentiation and their crosstalk with the biosynthesis of different secondary metabolites that act as biochemical signals between the producer cells and also as communication signals with competing microorganisms (e.g., antimicrobial agents or plant elicitors).