Opinion in 2008

Although most eukaryotic proteins are secreted through the conventional endoplasmic reticulum–Golgi secretory pathway, both cytoplasmic and nuclear proteins have been shown to reach the cell surface by non-conventional transport pathways. The mechanisms and molecular components of unconventional protein secretion are beginning to emerge.

Proto-oncogenic pathways, including the insulin-like growth factor-I (IGF-I), Ras and AKT/PKB pathways, have recently been implicated in the ageing process. In simple organisms, proto-oncogene homologues increase DNA damage, whereas in mice they increase cancer incidence. So, can we prevent cancer by chronic downregulation of pro-ageing pathways?

The question of whether cell death can occur by autophagy cannot yet be answered definitively, although the occurrence of cell death with autophagy is common. The term autophagic cell death should therefore be considered a misnomer until this issue has been resolved.

Cell-cycle transitions in higher eukaryotes are regulated by different cyclin-dependent kinases (CDKs) and cyclins. Recent work using gene-targeted mice has led to a revision of this model and revealed overlapping and essential roles of different CDKs and cyclins.

The 'histone code' hypothesis has inspired rapid advances throughout chromatin biology, and has recently been tapped for its relevance to non-histone proteins. What is the evidence that supports the existence of a protein code? And can this code be used to predict downstream events?

MYCis a potent oncogene that functions as a transcription factor. Extensive research has focused on the mechanism of MYC-induced transcription and on the identification of MYC transcriptional target genes. But does MYC also have transcription-independent roles?

Membrane blebs are considered to be a hallmark of apoptosis; however, blebs are also observed in healthy cells during cytokinesis and cell motility. What are the potential mechanisms by which blebbing can be polarized and translated into movement? And what are the advantages of blebbing motility?

Tumour-necrosis factor receptor-1 (TNFR1) and CD95 can transduce pro-apoptotic and anti-apoptotic signals, but what determines the specificity of signalling events? It is possible that the endosomal compartment functions as a signalling organelle that selectively transmits death signals from TNFR1 and CD95.

Although DNA replication is fundamental to the propagation of cellular life, the bacterial replication machinery is distinct from that used by archaea and eukaryotes. What has been the role of lateral gene transfer by extra-chromosomal elements in shaping the replication machinery during evolution?

Sorting nexins are associated with the early endosomal network and have important functions in endocytosis, sorting and signalling. But how do specific sorting nexins regulate tubular-based endosomal sorting and how do other sorting nexins coordinate sorting with endosomal signalling events?

Deadenylases shorten mRNA poly(A) tails and thereby regulate mRNA translation and decay. Recent studies have shown that these factors form different complexes. The recruitment of multifunctional deadenylase complexes to target mRNAs provides a unique node to control mRNA translation and decay.

The structural maintenance of chromosomes (Smc)5/6 complex has a poorly characterized role in DNA repair. Smc5/6 has been implicated specifically in rDNA stability, but the authors propose that the unidirectional replication of rDNA merely accentuates the genome-wide functions of Smc5/6 in repairing DNA replication errors.