Summary Spatial control of gene expression, at the level of both transcription and translation, is critical for cellular differentiation [1-4]. In budding yeast, the conserved Ndr/warts kinase Cbk1 localizes to the new daughter cell where it acts as a cell fate determinant. Cbk1 both induces a daughter-specific transcriptional program and promotes morphogenesis in a less well-defined role [5-8]. Cbk1 is essential in cells expressing functional Ssd1, an RNA binding protein of unknown function [9-11]. We show that Cbk1 inhibits Ssd1 in vivo. Loss of this regulation dramatically slows bud expansion, leading to highly aberrant cell wall organization at the site of cell growth. Ssd1 associates with specific mRNAs, a significant number of which encode cell wall remodeling proteins. Translation of these messages is rapidly and specifically suppressed when Cbk1 is inhibited; this suppression requires Ssd1. Transcription of several of these Ssd1-associated mRNAs is also regulated by Cbk1, indicating that the kinase controls both the transcription and translation of daughter-specific mRNAs. This work suggests a novel system by which cells coordinate localized expression of genes involved in processes critical for cell growth and division.

The budding yeast regulation of Ace2 and morphogenesis (RAM) network integrates cell fate determination and morphogenesis. Its disruption impairs polarized growth and causes mislocalization of the transcription factor Ace2, resulting in failure of daughter cell–specific transcription required for cell separation. We find that phosphoregulation of the conserved AGC family kinase Cbk1 is critical for RAM network function. Intramolecular autophosphorylation of the enzyme's activation loop is critical for kinase activity but is only partially required for cell separation and polarized growth. In marked contrast, phosphorylation of a C-terminal hydrophobic motif is required for Cbk1 function in vivo but not for its kinase activity, suggesting a previously unappreciated level of control for this family of kinases. Phosphorylation of the C-terminal site is regulated over the cell cycle and requires the transcription factor Ace2 as well as all RAM network components. Therefore, Ace2 is not only a downstream target of Cbk1 but also reinforces activation of its upstream regulator.

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Opposing cellular responses are typically regulated by distinct sets of genes. However, tissue transglutaminase (TGase) provides an interesting example of a single gene product that has been implicated both in affording protection against cellular insults as well as in promoting cell death. Here, we shed some light on how these conflicting activities might be manifested by demonstrating that alternative transcripts of TGase differentially affect cell viability. We show that although the full-length TGase protein affords strong protection against cell death signals, a shorter version of TGase that is truncated at the 3 end, and thus called TGase-short (TGase-S), is cytotoxic. The apoptotic activity of TGase-S is not dependent on its transamidation activity because the mutation of a cysteine residue that is essential for catalyzing this reaction does not compromise the ability of TGase-S to induce cell death. Intriguingly, TGase-S undergoes inappropriate oligomer formation in cells before cell death, suggesting a novel mechanism for the apoptotic effects of this protein.aggregation ͉ cell death ͉ transamidation

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