Certain tumors are dependent on autophagy for survival; thus, the use of unc‐51‐like autophagy activating kinase (ULK) 1 inhibitors to block autophagy has the potential for tumor treatment. However, ULK1 inhibitors affect processes other than autophagy. Herein, we report that the ULK1 inhibitors SBI‐0206965/MRT68921 not only inhibit phosphorylation of histone H3 (Ser10) and delay chromatin condensation but also induce spindle microtubule disorganization to form short and fragmented microtubule polymers. Although the delay in chromatin condensation also delayed mitotic entry, the disorganized microtubule polymers resulted in unsegregated chromosomes and polyploidy. Although the effect on mitotic entry was moderate, polyploidy formation was decreased in ULK1 knockout cells with or without ULK2 knockdown. In conclusion, it will be helpful to consider the roles of ULK1 inhibitors in mitotic dysregulation, as well as autophagy, when evaluating their antitumor efficacy.

中文翻译：

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ULK1抑制剂诱导纺锤体微管解体并抑制组蛋白H3 Ser10的磷酸化

某些肿瘤依赖自噬生存；因此，使用类 unc-51 自噬激活激酶 (ULK) 1 抑制剂来阻断自噬具有治疗肿瘤的潜力。然而，ULK1 抑制剂影响自噬以外的过程。在此，我们报告了 ULK1 抑制剂 SBI-0206965/MRT68921 不仅抑制组蛋白 H3 (Ser10) 的磷酸化并延迟染色质凝聚，而且还诱导纺锤体微管解体形成短而碎片化的微管聚合物。尽管染色质凝聚的延迟也延迟了有丝分裂的进入，但杂乱无章的微管聚合物导致了未分离的染色体和多倍体。尽管对有丝分裂进入的影响是中等的，但在有或没有 ULK2 敲低的情况下，ULK1 敲除细胞中的多倍体形成减少。综上所述，