RESUMEN
Aluminum (Al) toxicity is one of the major constraints for crop production in acid soils, Al-ACTIVATED MALATE TRANSPORTER1 (ALMT1)-dependent malate exudation from roots is essential for Al resistance in Arabidopsis, in which the C2H2-type transcription factor SENSITIVE TO PROTONRHIZOTOXICITY1 (STOP1) play a critical role. In this study, we reveal that the RAE1-GL2-STOP1-RHD6 protein module regulated the ALMT1-mediated Al resistance. GL2, STOP1 and RHD6 directly target the promoter of ALMT1 to suppress or activate its transcriptional expression, respectively, and mutually influence their action on the promoter of ALMT1 by forming a protein complex. STOP1 mediates the expression of RHD6 and RHD6-regulated root growth inhibition, while GL2 and STOP1 suppress each other's expression at the transcriptional and translational level and regulate Al-inhibited root growth. F-box protein RAE1 degrades RHD6 via the 26S proteasome, leading to suppressed activity of the ALMT1 promoter. RHD6 inhibits the transcriptional expression of RAE1 by directly targeting its promoter. Unlike RHD6, RAE1 promotes the GL2 expression at the protein level and GL2 activates the expression of RAE1 at the transcriptional level by directly targeting its promoter. The study provides insights into the transcriptional regulation of ALMT1, revealing its significance in Al resistance and highlighting the crucial role of the STOP1-associated regulatory networks.
Asunto(s)
Aluminio , Proteínas de Arabidopsis , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Raíces de Plantas , Regiones Promotoras Genéticas , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Aluminio/toxicidad , Aluminio/metabolismo , Raíces de Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/genética , Regiones Promotoras Genéticas/genética , Transportadores de Anión Orgánico/metabolismo , Transportadores de Anión Orgánico/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Plantas Modificadas GenéticamenteRESUMEN
Background: The accurate assessment of residual tumor tissue after neoadjuvant chemotherapy (NAC) for breast cancer is closely related to the subsequent treatment and prognosis of patients. The objective of this study is to develop a new pathological assessment metric for breast cancer patients through combining residual disease in breast and nodes (RDBN) and the Ki-67 expression status after NAC. We call the new metric residual disease in breast and nodes combined with Ki-67 (RDBN-K) and aim to study its significance for prognosis. Methods: A total of 723 breast cancer patients with TNM staging II to III who received NAC and surgical treatment underwent residual disease evaluation by RDBN-K and RDBN. All patients were followed up for a median of 44 months. We used pairwise stratified analysis to compare the accuracy and clinical significance of the RDBN and RDBN-K. Results: Pairwise stratified analysis revealed that DFS and OS had larger difference between RDBN-K-3 and RDBN-K-4 compared to between RDBN-3 and RDBN-4. Moreover, RDBN-K also showed larger differences in OS between stage 2 and 3 compared to RDBN alone. Conclusions: Incorporating Ki-67 expression status into RDBN improved the accuracy in residual tumor burden assessment after NAC. RDBN-K is a better metric for predicting treatment outcomes and identify patients who warrant follow-up intensive treatment.