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LIMD 1 phosphorylation in mitosis is required for mitotic progression and its tumor‐suppressing activity
Author(s) -
Zhou Jiuli,
Zhang Lin,
Zhou Wei,
Chen Yuanhong,
Cheng Yufeng,
Dong Jixin
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14743
Subject(s) - mitosis , phosphorylation , cyclin dependent kinase 1 , microbiology and biotechnology , kinase , biology , cell growth , cell cycle , cyclin dependent kinase , cancer research , cell , genetics
LIM domains containing 1 ( LIMD 1) is a member of the Zyxin family proteins and functions as a tumor suppressor in lung cancer. LIMD 1 has been shown to regulate Hippo‐ YAP signaling activity. Here, we report a novel regulatory mechanism for LIMD 1. We found that cyclin‐dependent kinase 1 ( CDK 1) and c‐Jun NH 2‐terminal kinases 1/2 ( JNK 1/2) phosphorylate LIMD 1 in vitro and in cells during anti‐tubulin drug‐induced mitotic arrest. Phosphorylation also occurs during normal mitosis. S272, S277, S421, and S424 were identified as the main phosphorylation sites in LIMD 1. Deletion of LIMD 1 resulted in a shortened mitotic cell cycle and phosphorylation of LIMD 1 is required for proper mitotic progression. We further showed that the phosphorylation‐deficient mutant LIMD 1‐4A is less active in suppressing cell proliferation, anchorage‐independent growth, cell migration, and invasion in lung cancer cells. Together, our findings suggest that LIMD 1 is a key regulator of mitotic progression, and that dysregulation of LIMD 1 contributes to tumorigenesis.