CONSTITUTIVELY PHOTOMORPHOGENIC1 promotes ABA-mediated inhibition of post-germination seedling establishment.

Under acute stress conditions, precocious seedling development may result in the premature death of young seedlings, before they switch to autotrophic growth. The phytohormone abscisic acid (ABA) inhibits seed germination and post-germination seedling establishment under unfavorable conditions. Various environmental signals interact with the ABA pathway to optimize these early developmental events under stress. Here, we show that light availability critically influences ABA sensitivity during early seedling development. In dark conditions, the ABA-mediated inhibition of post-germination seedling establishment is strongly enhanced. COP1, a central regulator of seedling development in the dark, is necessary for this enhanced post-germination ABA sensitivity in darkness. Despite their slower germination, cop1 seedlings establish faster than wild type in the presence of ABA in both light and dark. PHY and CRY photoreceptors that inhibit COP1 activity in light modulate ABA-mediated inhibition of seedling establishment in light. Genetically, COP1 acts downstream to ABI5, a key transcriptional regulator of ABA signaling, and does not influence the transcriptional and protein levels of ABI5 during the early post-germination stages. COP1 promotes post-germination growth arrest independent of the antagonistic interaction between ABA and cytokinin signaling pathways. COP1 facilitates the binding of ABI5 on its target promoters and the ABA-mediated upregulation of these target genes is reduced in cop1-4. Together, our results suggest that COP1 positively regulates ABA signaling to inhibit post-germination seedling establishment under stress.

DEPTOR promotes survival of cervical squamous cell carcinoma cells and its silencing induces apoptosis through downregulating PI3K/AKT and by up-regulating p38 MAP kinase.

DEPTOR is an endogenous inhibitor of mTOR complexes, de-regulated in cancers. The present study reveals a vital role for DEPTOR in survival of cervical squamous cell carcinoma (SCC). DEPTOR was found to be overexpressed in both cervical SCC cells and tissues and it's silencing in cervical SCC cells induced apoptosis, mainly by up-regulation of p38 MAPK and by inhibiting PI3K/AKT pathway via a feed-back inhibition from mTORC1-S6K. DEPTOR silencing resulted in reduced expression of the nitric oxide synthases iNOS and eNOS, as well as increased activation of ERK1/2 and p38 MAP kinases. Activation of AKT signaling by overexpression of constitutively active-AKT (CA-AKT) failed to overcome the apoptosis caused by DEPTOR silencing. Similarly pharmacological inhibition of ERK also failed to control apoptosis. However pharmacological inhibition of p38 MAPK rescued the cells from apoptosis, indicating the major role of p38 MAPK in cell death induced by DEPTOR silencing. DEPTOR was also found to regulate ERK1/2 in an AKT dependent manner. DEPTOR knockdown induced cell death in SiHa cells overexpressing the anti-apoptotic Bcl-2 and Bcl-xL, indicating strong survival role of DEPTOR in these cells. DEPTOR overexpression activated PI3K/AKT by relieving the negative feed-back inhibition from mTORC1-S6K. DEPTOR regulation was also observed to be independent of HPV E6/E7 oncoproteins, but it might be a molecular co-factor contributing to cervical carcinogenesis. In summary, DEPTOR is found to promote survival of cervical SCC cells and its reduction induced apoptosis via differential effects on PI3K/AKT and p38 MAPK and can be a potential target in cervical SCC.