c-Jun is essential for organization of the epidermal leading edge.

The migration of epithelial layers requires specific and coordinated organization of the cells at the leading edge of the sheet. Mice that are conditionally deleted for the c-jun protooncogene in epidermis are born at expected frequencies, but with open eyes and with defects in epidermal wound healing. Keratinocytes lacking c-Jun are unable to migrate or elongate properly in culture at the border of scratch assays. Histological analyses in vitro and in vivo demonstrate an inability to activate EGF receptor at the leading edge of wounds, and we demonstrate that this can be rescued by supplementation with conditioned medium or the EGF receptor ligand HB-EGF. Lack of c-Jun prevents EGF-induced expression of HB-EGF, indicating that c-jun controls formation of the epidermal leading edge through its control of an EGF receptor autocrine loop.

AGL24 acts as a promoter of flowering in Arabidopsis and is positively regulated by vernalization.

MADS-domain-containing transcription factors comprise a large family of regulators that have diverse roles in plant development, including the regulation of flowering time. AGAMOUS-LIKE 20/SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) and FRUITFUL act to promote flowering, whereas FLOWERING LOCUS C (FLC), FLOWERING LOCUS M/MADS AFFECTING FLOWERING1, and SHORT VEGETATIVE PHASE are inhibitors of flowering. Here we report that AGAMOUS-LIKE 24 (AGL24) also plays a role in the regulation of flowering time. agl24 mutants are late flowering and overexpression of AGL24 causes early flowering in wild-type and late-flowering-mutant backgrounds. The effect of AGL24 overexpression is most pronounced in autonomous-pathway-mutant and FRIGIDA-containing backgrounds. The behavior of AGL24 is most similar to that of SOC1. Like SOC1, AGL24 mRNA levels are upregulated by vernalization. Unlike SOC1, however, AGL24 mRNA levels are not affected by FLC, and therefore AGL24 may represent an FLC-independent target of the vernalization pathway. There is also evidence for cross-talk between AGL24 and SOC1. When overexpressed, SOC1 and AGL24 are able to upregulate each other's expression. Thus, AGL24 represents another component in a network of MADS-domain-containing transcription factors that regulate flowering time.

The response of c-jun/AP-1 to chronic hypoxia is hypoxia-inducible factor 1 alpha dependent.

Hypoxia (low-oxygen tension) is an important physiological stress that influences responses to a wide range of pathologies, including stroke, infarction, and tumorigenesis. Prolonged or chronic hypoxia stimulates expression of the stress-inducible transcription factor gene c-jun and transient activation of protein kinase and phosphatase activities that regulate c-Jun/AP-1 activity. Here we describe evidence obtained by using wild-type and HIF-1 alpha nullizygous mouse embryonic fibroblasts (mEFs) that the induction of c-jun mRNA expression and c-Jun phosphorylation by prolonged hypoxia are completely dependent on the presence of the oxygen-regulated transcription factor hypoxia-inducible factor 1 alpha (HIF-1 alpha). In contrast, transient hypoxia induced c-jun expression in both types of mEFs, showing that the early or rapid induction of this gene is independent of HIF-1 alpha. These findings indicate that the c-jun gene has a biphasic response to hypoxia consisting of inductions that depend on the degree or duration of exposure. To more completely define the relationship between prolonged hypoxia and c-Jun phosphorylation, we used mEFs from mice containing inactivating mutations of critical phosphorylation sites in the c-Jun N-terminal region (serines 63 and 73 or threonines 91 and 93). Exposure of these mEFs to prolonged hypoxia demonstrated an absolute requirement for N-terminal sites for HIF-1 alpha-dependent phosphorylation of c-Jun. Taken together, these findings suggest that c-Jun/AP-1 and HIF-1 cooperate to regulate gene expression in pathophysiological microenvironments.