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TAX1BP3 es una proteína de transporte nucleocitoplasmático sumoilada y protege contra la hiperplasia vascular

Hanyan Yang^1,2, Yulong Zhong³, Wenjie Guo^1,2

¹Department of Cardiology, Laboratory of Heart Center, Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China (H.Y., Wenjie Guo, Wenjing Guo, B.C., Z.L., X.C., J.Y., Z.Z., S.A., C.L.).

|September 16, 2025

Resumen

La proteína TAX1BP3, esencial para la función de las células del músculo liso vascular (VSMC), se SUMOila para regular su localización nuclear. Esta proteína previene la hiperplasia neointimal mediante la inhibición de la proliferación de VSMC a través de la interacción con YAP-TEAD.

Área de la Ciencia:

Biología vascular
Biología celular molecular
La bioquímica

Sus antecedentes:

La hiperplasia neointimal es una causa primaria de complicaciones vasculares después de las intervenciones arteriales, lo que plantea un desafío a pesar de las estrategias actuales.
Las interacciones proteína-proteína mediadas por el dominio PDZ son cruciales en los procesos biológicos, pero su papel en la formación de neointima es en gran medida inexplorado.
TAX1BP3, una proteína PDZ única, se investiga por su papel en el cambio fenotípico de las células musculares lisas vasculares (VSMC) y la hiperplasia neointimal.

Objetivo del estudio:

Investigar el papel de TAX1BP3 en el cambio fenotípico de VSMC.
Para aclarar la implicación de TAX1BP3 en la hiperplasia neointimal.
Comprender los mecanismos moleculares subyacentes a la función de TAX1BP3 en la enfermedad vascular.

Principales métodos:

Evaluación de la localización subcelular de TAX1BP3 en CMV y arterias de ratón.
Construcción de mutantes TAX1BP3 para estudiar el efecto de la SUMOilación en el transporte nucleocitoplasmático.
Generación de ratones Tax1bp3 de nocaut específicos para el VSMC y uso de un modelo de lesión del cable de la arteria carótida.
Integración de la secuenciación de ARN y ATAC-seq, predicción de la estructura computacional y coinmunoprecipitación.
Estudios in vivo con entrega de genes mediada por AAV y TAX1BP3 nanoencapsulado.

Principales resultados:

TAX1BP3 exhibe transporte nucleocitoplasmático dinámico durante el cambio fenotípico VSMC, regulado por SUMOilación en K116.
La deficiencia de TAX1BP3 promueve la transición de VSMC a un fenotipo sintético y exacerba la hiperplasia neoinimal.
TAX1BP3 regula el ciclo celular VSMC y la proliferación a través de la actividad de transcripción YAP-TEAD, compitiendo con la unión YAP de una manera no canónica PDZ.
La administración de genes y la nanoencapsulación de TAX1BP3 reducen significativamente la hiperplasia neointimal y la progresión de la aterosclerosis.

Conclusiones:

La SUMOilación de TAX1BP3 en K116 es crítica para su transporte nucleocitoplasmático y su papel protector en el cambio fenotípico de VSMC.
TAX1BP3 interactúa competitivamente con YAP-TEAD, inhibiendo la proliferación de VSMC y mitigando la hiperplasia neointimal.
TAX1BP3 representa un objetivo terapéutico potencial para prevenir complicaciones vasculares como la hiperplasia neointimal y la aterosclerosis.

Palabras clave:

Dominios de las ZPD Enfermedades arteriales Proliferación de las células lesiones vasculares músculo liso vascular

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