Volume 7 Issue 3, March 2005

In this issue, two groups have examined the role of the Par proteins in the regulation of small G proteins, in two different models of cell polarity — mammalian epithelia and neuronal axon specification. They concurrently report the intriguing finding that the Par-3/Par-6/aPKC complex can regulate the activation of Rac by interaction with the guanine nucleotide exchanger, Tiam1/STEF. Furthermore, they also demonstrate a hitherto under-appreciated role for the Par-3/Par-6/aPKC complex in the regulation of the actin cytoskeleton.

Targeting substrates to the proteasome is generally thought to depend on long polyubiquitin chains that form on the substrate. Recent work has led to the provocative proposal that some substrates may be targeted to the proteasome through smaller chains that contain only four to six ubiquitin molecules.

Actin polymerization is intimately associated with endocytosis in yeast and mammalian cells. Mechanisms of actin filament assembly in endocytosis are becoming better understood but less is known about how assembly is terminated. In yeast, phosphorylation of Arp2/3 complex activators provides one mechanism for downregulating endocytic actin assembly.

Nuclear accumulation of the c-Abl tyrosine kinase is associated with a pro-apoptotic response after DNA damage, but the mechanism regulating c-Abl nuclear localization is unclear. DNA damage and other stress signals are now shown to induce phosphorylation of 14-3-3 proteins by the c-Jun amino-terminal kinase, disrupting a c-Abl/14-3-3 cytoplasmic complex, and liberating c-Abl for translocation to the nucleus.

Cancer cells have a raised cellular metabolism, including increased protein biosynthesis. Three new studies now show that the oncoprotein Myc, known to drive cell division, also enhances ribosomal RNA synthesis by RNA polymerase I in addition to controlling RNA polymerase II- and III-regulated gene transcription. This suggests that Myc promotes the generation of crucial components of a functional ribosome.