At the end of abscission, the residual midbody forms the so-called midbody remnant (MBR), a platform affecting cell fate with emerging key role in differentiation, development, and tumorigenicity. Depending on cell type and pathophysiological context, MBRs undergo different outcomes: they can be retained, released, internalized by nearby cells, or removed through autophagy-mediated degradation. Although mechanisms underlying MBR formation, positioning, and processing have been recently identified, their regulation is still largely unknown. Here, we report that the multifunctional kinase HIPK2 regulates MBR processing contributing to MBR removal. In the process of studying the role of HIPK2 in abscission, we observed that, in addition to cytokinesis failure, HIPK2 depletion leads to significant accumulation of MBRs. In particular, we detected comparable accumulation of MBRs after HIPK2 depletion or treatment with the autophagic inhibitor chloroquine. In contrast, single depletion of the two independent HIPK2 abscission targets, extrachromosomal histone H2B and severing enzyme Spastin, only marginally increased MBR retention, suggesting that MBR accumulation is not just linked to cytokinesis failure. We found that HIPK2 depletion leads to (i) increased levels of CEP55, a key effector of both midbody formation and MBR degradation; (ii) decreased levels of the selective autophagy receptors NBR1 and p62/SQSTM1; and (iii) impaired autophagic flux. These data suggest that HIPK2 contributes to MBR processing by regulating its autophagy-mediated degradation.

脱落结束时，残留的中体形成所谓的中体残基（MBR），该平台影响细胞命运，并在分化，发育和致瘤性中起着关键作用。取决于细胞类型和病理生理背景，MBR经历不同的结果：它们可以被保留，释放，被附近的细胞内化，或通过自噬介导的降解而被去除。尽管最近已经确定了MBR形成，定位和处理的基础机制，但是它们的调控仍然很大程度上未知。在这里，我们报告多功能激酶HIPK2调节MBR加工，有助于去除MBR。在研究HIPK2在脱落中的作用的过程中，我们观察到，除了胞质分裂失败之外，HIPK2耗竭还导致MBR的大量积累。尤其是，我们检测到在HIPK2耗尽或用自噬抑制剂氯喹治疗后MBRs的积累量相当。相比之下，两个独立的HIPK2脱落靶标，染色体外组蛋白H2B和切断酶Spastin的单耗竭仅略微增加了MBR保留，这表明MBR积累不仅与胞质分裂失败有关。我们发现，HIPK2耗竭导致（i）CEP55水平升高，CEP55是中体形成和MBR降解的关键效应子；（ii）选择性自噬受体NBR1和p62 / SQSTM1的水平降低；（iii）自噬通量受损。这些数据表明，HIPK2通过调节其自噬介导的降解而有助于MBR加工。两个独立的HIPK2脱落靶标，染色体外组蛋白H2B和切断酶Spastin的单耗，仅略微增加了MBR保留，这表明MBR积累不仅与胞质分裂失败有关。我们发现，HIPK2耗竭导致（i）CEP55水平升高，CEP55是中体形成和MBR降解的关键效应子；（ii）选择性自噬受体NBR1和p62 / SQSTM1的水平降低；（iii）自噬通量受损。这些数据表明，HIPK2通过调节其自噬介导的降解而有助于MBR加工。两个独立的HIPK2脱落靶标，染色体外组蛋白H2B和切断酶Spastin的单耗，仅略微增加了MBR保留，这表明MBR积累不仅与胞质分裂失败有关。我们发现，HIPK2耗竭导致（i）CEP55水平升高，CEP55是中体形成和MBR降解的关键效应子；（ii）选择性自噬受体NBR1和p62 / SQSTM1的水平降低；（iii）自噬通量受损。这些数据表明，HIPK2通过调节其自噬介导的降解而有助于MBR加工。我们发现，HIPK2耗竭导致（i）CEP55水平升高，CEP55是中体形成和MBR降解的关键效应子；（ii）选择性自噬受体NBR1和p62 / SQSTM1的水平降低；（iii）自噬通量受损。这些数据表明，HIPK2通过调节其自噬介导的降解而有助于MBR加工。我们发现，HIPK2耗竭导致（i）CEP55水平升高，CEP55是中体形成和MBR降解的关键效应子；（ii）选择性自噬受体NBR1和p62 / SQSTM1的水平降低；（iii）自噬通量受损。这些数据表明，HIPK2通过调节其自噬介导的降解而有助于MBR加工。