The Jun N-terminal kinases (JNKs) recently have been shown to be required for thymocyte apoptosis and T cell differentiation and͞or proliferation. To investigate the molecular targets of JNK signaling in lymphoid cells, we used mice in which the serines phosphorylated by JNK in c-Jun were replaced by homologous recombination with alanines (junAA mice). Lymphocytes from these mice showed no phosphorylation of c-Jun in response to activation stimuli, whereas c-Jun was rapidly phosphorylated in wild-type cells. Despite the fact that c-jun is essential for early development, junAA mice develop normally; however, c-Jun N-terminal phosphorylation was required for efficient T cell receptor-induced and tumor necrosis factor-␣-induced thymocyte apoptosis. In contrast, c-Jun phosphorylation by JNK is not required for T cell proliferation or differentiation. Because jnk2؊͞؊ T cells display a proliferation defect, we concluded that JNK2 must have other substrates required for lymphocyte function. Surprisingly, jnk2؊͞؊ T cells showed reduced NF-AT DNA-binding activity after activation. Furthermore, overexpression of JNK2 in Jurkat T cells strongly enhanced NF-AT-dependent transcription. These results demonstrate that JNK signaling differentially uses c-Jun and NF-AT as molecular effectors during thymocyte apoptosis and T cell proliferation.

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Global mRNA translation may differ dramatically between progenitor cells and their differentiated progeny. One way cell type-specific translation is established is through ribosome concentration. In addition to addressing unique metabolic needs, changes in ribosome concentration may influence cell fate. The mechanisms that determine ribosome abundance in progenitors versus differentiated progeny are not fully understood. Here we investigated this process by focusing on ribosomal RNA (rRNA) synthesis in Drosophila neural progenitors and neurons. We found that rRNA synthesis is robust in neural progenitors but is limited in post-mitotic neurons. Newly born neurons inherit rRNA from their progenitor parent and this inherited rRNA is sufficient for protein synthesis in neurons. Our findings support a model in which neuron-specific translation programs are established by rRNA inheritance.