维生素B6是细胞类型和组织中必不可少的微量营养素，而B6水平失调会导致人类疾病。尽管其重要性，目前对于B6维生素水平的调节机制尚不清楚。在这里，我们提供证据表明，通过将吡哆醛激酶（PDXK），这种限制B6酶的速率，精确地分隔来迅速调节B6的动力学。我们发现规范的Wnt通路能够通过将细胞质中的PDXK重新定位到溶酶体中，从而迅速导致非活性B6的积累。PDXK被甲基精氨酸Degron（MrDegron），一种用于溶酶体的蛋白质标签，修饰，从而通过微自噬途径送至溶酶体。高活性的溶酶体导致持续降解PDXK并造成B6缺乏，从而促进Wnt驱动的结肠直肠癌（CRC）细胞的增殖。通过药理学或遗传学手段破坏协调的MrDegron蛋白酶解途径足以减少CRC细胞和器官样模型中的细胞存活。总之，这项研究为微量营养素调控的癌细胞生长过程提供了补充，并揭示了B6缺乏对生存的功能影响。

Vitamin B6 is a vital micronutrient across cell types and tissues, and dysregulated B6 levels contribute to human disease. Despite its importance, how B6 vitamer levels are regulated is not well understood. Here, we provide evidence that B6 dynamics are rapidly tuned by precise compartmentation of pyridoxal kinase (PDXK), the rate-limiting B6 enzyme. We show that canonical Wnt rapidly led to the accumulation of inactive B6 by shunting cytosolic PDXK into lysosomes. PDXK was modified with methyl-arginine Degron (MrDegron), a protein tag for lysosomes, which enabled delivery via microautophagy. Hyperactive lysosomes resulted in the continuous degradation of PDXK and B6 deficiency that promoted proliferation in Wnt-driven colorectal cancer (CRC) cells. Pharmacological or genetic disruption of the coordinated MrDegron proteolytic pathway was sufficient to reduce CRC survival in cells and organoid models. In sum, this work contributes to the repertoire of micronutrient-regulated processes that enable cancer cell growth and provides insight into the functional impact of B6 deficiencies for survival.