Haspin inhibition delays cell cycle progression through interphase in cancer cells

Haspin (Haploid Germ Cell‐Specific Nuclear Protein Kinase) is a serine/threonine kinase pertinent to normal mitosis progression and mitotic phosphorylation of histone H3 at threonine 3 in mammalian cells. Different classes of small molecule inhibitors of haspin have been developed and utilized to in...

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Veröffentlicht in:Journal of cellular physiology 2020-05, Vol.235 (5), p.4508-4519
Hauptverfasser: Wang, Peiling, Hua, Xiangmei, Bryner, Yuge Han, Liu, Sijing, Gitter, Christopher B., Dai, Jun
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Sprache:eng
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Zusammenfassung:Haspin (Haploid Germ Cell‐Specific Nuclear Protein Kinase) is a serine/threonine kinase pertinent to normal mitosis progression and mitotic phosphorylation of histone H3 at threonine 3 in mammalian cells. Different classes of small molecule inhibitors of haspin have been developed and utilized to investigate its mitotic functions. We report herein that applying haspin inhibitor CHR‐6494 or 5‐ITu at the G1/S boundary could delay mitotic entry in synchronized HeLa and U2OS cells, respectively, following an extended G2 or the S phase. Moreover, late application of haspin inhibitors at S/G2 boundary is sufficient to delay mitotic onset in both cell lines, thereby, indicating a direct effect of haspin on G2/M transition. A prolonged interphase duration is also observed with knockdown of haspin expression in synchronized and asynchronous cells. These results suggest that haspin can regulate cell cycle progression at multiple stages at both interphase and mitosis. Haspin (Haploid Germ Cell‐Specific Nuclear Protein Kinase) is a protein kinase required for normal mitosis progression. Using small molecular inhibitors of haspin, we found that haspin can regulate cell cycle progression at multiple stages at both interphase and mitosis.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.29328