Oomycetes, effectors, and all that jazz

Plant pathogenic oomycetes secrete a diverse repertoire of effector proteins that modulate host innate immunity and enable parasitic infection. Understanding how effectors evolve, translocate and traffic inside host cells, and perturb host processes are major themes in the study of oomycete-plant interactions. The last year has seen important progress in the study of oomycete effectors with, notably, the elucidation of the 3D structures of five RXLR effectors, and novel insights into how cytoplasmic effectors subvert host cells. In this review, we discuss these and other recent advances and highlight the most important open questions in oomycete effector biology.     

p53, Autophagy and tumor suppression

Autophagy was recently established as a novel tumor suppression mechanism, which stimulated a wave of investigations that were aimed at understanding exactly how autophagy prevents tumorigenesis, as well as to determine to what extent autophagy is implicated in human cancers. Autophagy might exert its tumor suppression function at the subcellular level by removing defective cytoplasmic components, such as damaged mitochondria. In addition, it might function at the cellular level by helping in the orderly removal of damaged cells. Previous studies indicated that autophagy is compromised in human breast, ovarian and prostate cancers. Recent research revealed that autophagy is activated by p53, a critical tumor suppressor that is involved in most, if not all, tumorigenesis. This study places autophagy in a broader context of human cancers. Future work elucidating the role of autophagy in the p53 circuit and p53 function might provide more insight into tumorigenesis and targeted cancer chemotherapy.     

Noise, delays, robustness, canalization and all that

A biological system such as a developing embryo can withstand many perturbations. What is the basis of this robustness both against noise and mutation? Recent advances in modeling may throw new light on this old problem. First, recent theoretical and experimental work clearly demonstrates the importance of noise and time delays for the proper functioning of genetic networks: noise and delays are simply part of the normal operating constraints. By contrast, sweeping statements have been made recently about a so-called 'robustness' of biological processes, based on work that neglects noise and delays completely. I submit that studying the stability of complex biological systems with such omissions is an unnecessary, inadequate and potentially disastrous simplification. I review the existing alternatives and propose using them to construct a modeling framework that overcomes all serious limitations.     

Stratigraphical classification and all that

Quantitative treatment of the geological sciences must remain limited; there continues to be need for a language of words. This is keenly felt in stratigraphy, where the practising geologist is dismayed by the effusions of the stratigraphical philosophers. The situation, in so far as it appears to remain in some ways obscure or troublesome, is briefly reviewed in terms of lithostratigraphy. biostratigraphy. and chronostratigraphy. A revised version of a controversial diagram is presented, in which the role of the boundary stratotype as anchor point is believed to be clarified. Finally a synthesis is attempted of relationships between the various stratigraphical procedures and the provision of dates in years through the parallel discipline of geochronometry.     

Role of JNK in tumor development

The c-Jun NH2-terminal kinase (JNK) is implicated in oncogenic transformation. However, studies of the effect of Jnk gene disruption on Ras-induced transformation of murine fibroblasts indicate that JNK may act as a suppressor of Ras transformation and that the JNK signaling pathway contributes to the apoptotic elimination of transformed cells in vivo. The conclusion that JNK can act as a tumor suppressor is consistent with the presence of loss-of-function mutations in JNK pathway components (Jnk3 and Mkk4) in human tumors. Nevertheless, JNK can also contribute to the proliferation and survival responses of some tumors. A key question that remains unresolved concerns the genetic and mechanistic basis for these different roles of JNK in tumors. Indeed, an understanding of this question will be required for the rational use of small molecule inhibitors of JNK for tumor therapy.     

Secreting tumor suppression

Cellular senescence limits the proliferative capacity of damaged cells and thereby acts as an intrinsic mechanism of tumor suppression. In this issue, Wajapeyee et al. (2008) identify insulin growth factor binding protein 7 (IGFBP7) as a secreted factor that mediates senescence induced by oncogenic BRAF in normal melanocytes. In addition, IGFBP7 triggers apoptosis in cells that have progressed to melanoma, suggesting a new approach for melanoma treatment.     

Oncogenic and tumor suppressor function of MEIS and associated factors

MEIS proteins are historically associated with tumorigenesis, metastasis, and invasion in cancer. MEIS and associated PBX-HOX proteins may act as tumor suppressors or oncogenes in different cellular settings. Their expressions tend to be misregulated in various cancers. Bioinformatic analyses have suggested their upregulation in leukemia/lymphoma, thymoma, pancreas, glioma, and glioblastoma, and downregulation in cervical, uterine, rectum, and colon cancers. However, every cancer type includes, at least, a subtype with high MEIS expression. In addition, studies have highlighted that MEIS proteins and associated factors may function as diagnostic or therapeutic biomarkers for various diseases. Herein, MEIS proteins and associated factors in tumorigenesis are discussed with recent discoveries in addition to how they could be modulated by noncoding RNAs or newly developed small-molecule MEIS inhibitors.