title: C-Terminus of Hsc70-interacting protein regulates profilin1 and breast cancer cell migration.
abstract: Profilin1 (Pfn1) is a key mediator of actin polymerization and regulates cell migration. Low expression of Pfn1 is implicated in tumorigenesis of various cancers, including breast cancer. The regulatory mechanism behind Pfn1 levels has not yet been elucidated. In the present study, we find that Pfn1 is poly-ubiquitinated in human cell lines, and a portion of poly-ubiquitinated Pfn1 is regulated in a proteasome-dependent manner. C-terminus of Hsc70-interacting protein (CHIP), a co-chaperone E3 ligase, interacts with and ubiquitinates Pfn1, targeting it for proteasome-dependent degradation. Depletion of CHIP stabilizes Pfn1, suggesting that CHIP functions as a major E3 ligase for Pfn1. Stable expression of wild-type CHIP in the breast cancer cell line MDA-MB231 yielded downregulation of Pfn1 and enhanced cell migration. Pfn1 overexpression in MDA-MB231 cells expressing wild-type CHIP suppressed the enhanced cell migration. Taken together, our results demonstrate that CHIP regulates Pfn1 levels as an E3 ligase, and possibly plays a role in cell migration and metastasis of breast cancer.
authors.affiliation: Department of Biology, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Ye Na
authors.initials: YN
authors.lastname: Choi
authors.affiliation: Department of Nanopharmaceutical Life Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Sun Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Biology, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Tae Woong
authors.initials: TW
authors.lastname: Seo
authors.affiliation: Department of Nanopharmaceutical Life Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Biology, Kyung Hee University, Seoul 130-701, Republic of Korea; Department of Nanopharmaceutical Life Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: yoosoonji@khu.ac.kr.
authors.forename: Soon Ji
authors.initials: SJ
authors.lastname: Yoo
mesh_terms: D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D057809:HEK293 Cells; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D051304:Profilins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D060066:Protein Interaction Maps; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D050883:HSC70 Heat-Shock Proteins; C495738:PFN1 protein, human; D051304:Profilins; C467728:STUB1 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: Breast cancer; CHIP; Cell migration; Pfn1; Ubiquitin proteasome system