Lee, Kyung Ho Hwang, Jeong-Ah Kim, Sun-Ok Kim, Jung Hee Shin, Sang Chul Kim, Eunice EunKyeong Lee, Kyung S. Rhee, Kunsoo Jeon, Byeong Hwa Bang, Jeong Kyu Cha-Molstad, Hyunjoo Soung, Nak-Kyun Jang, Jae-Hyuk Ko, Sung-Kyun Lee, Hee Gu Ahn, Jong Seog Kwon, Yong Tae Kim, Bo Yeon 2024-01-19T23:33:02Z 2024-01-19T23:33:02Z 2021-09-03 2018-01-19 0021-9258 https://pubs.kist.re.kr/handle/201004/121800 Elevated expression of human enhancer filamentation 1 (HEF1;also known as NEDD9 or Cas-L) is an essential stimulus for the metastatic process of various solid tumors. This process requires HEF1 localization to focal adhesions (FAs). Although the association of HEF1 with FAs is considered to play a role in cancer cell migration, the mechanism targeting HEF1 to FAs remains unclear. Moreover, up-regulation of Polo-like kinase 1 (Plk1) positively correlates with human cancer metastasis, yet how Plk1 deregulation promotes metastasis remains elusive. Here, we report that casein kinase 1 delta (CK1 delta) phosphorylates HEF1 at Ser-780 and Thr-804 and that these phosphorylation events promote a physical interaction between Plk1 and HEF1. We found that this interaction is critical for HEF1 translocation to FAs and for inducing migration of HeLa cells. Plk1-docking phosphoepitopes were mapped/ confirmed in HEF1 by various methods, including X-ray crystallography, and mutated for functional analysis in HeLa cells. In summary, our results reveal the role of a phosphorylation-dependent HEF1-Plk1 complex in HEF1 translocation to FAs to induce cell migration. Our findings provide critical mechanistic insights into the HEF1-Plk1 complex-dependent localization of HEF1 to FAs underlying the metastatic process and may therefore contribute to the development of new cancer therapies. English AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC MOLECULAR-BASIS BOX DOMAIN METASTASIS CENTROSOME PLASTICITY INVASION GROWTH PHENIX Phosphorylation of human enhancer filamentation 1 (HEF1) stimulates interaction with Polo-like kinase 1 leading to HEF1 localization to focal adhesions Article 10.1074/jbc.M117.802587 1 JOURNAL OF BIOLOGICAL CHEMISTRY, v.293, no.3, pp.847 - 862 JOURNAL OF BIOLOGICAL CHEMISTRY 293 3 847 862 scie scopus 000422864500008 2-s2.0-85041008027 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article MOLECULAR-BASIS BOX DOMAIN METASTASIS CENTROSOME PLASTICITY INVASION GROWTH PHENIX