C-terminus of Hsc70-interacting protein regulates profilin1 and breast cancer cell migration

Ye Na Choi; Sun Kyung Lee; Tae Woong Seo; Ji Sun Lee; Soon Ji Yoo

doi:10.1016/j.bbrc.2014.03.061

C-terminus of Hsc70-interacting protein regulates profilin1 and breast cancer cell migration

Ye Na Choi
, Sun Kyung Lee
, Tae Woong Seo
, Ji Sun Lee
, Soon Ji Yoo

Research output: Contribution to journal › Article › peer-review

30 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1060-1066
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	446
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2014.03.061
Publication status	Published - 18 Apr 2014

Bibliographical note

Funding Information:
We are grateful to Dr. Lee K.H. at Chosun University for the kind gift of VN173 and VC155 constructs used for BiFC assays. This work was supported by the National Research Foundation (NRF) ( 2009-0077619 , 2009-0070405 ). J.S.L. was supported by a Brain Korea 21 Research Fellowship from the Korean Ministry of Education .

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Breast cancer
CHIP
Cell migration
Pfn1
Ubiquitin proteasome system

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10.1016/j.bbrc.2014.03.061

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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.",

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author = "Choi, \{Ye Na\} and Lee, \{Sun Kyung\} and Seo, \{Tae Woong\} and Lee, \{Ji Sun\} and Yoo, \{Soon Ji\}",

note = "Funding Information: We are grateful to Dr. Lee K.H. at Chosun University for the kind gift of VN173 and VC155 constructs used for BiFC assays. This work was supported by the National Research Foundation (NRF) ( 2009-0077619 , 2009-0070405 ). J.S.L. was supported by a Brain Korea 21 Research Fellowship from the Korean Ministry of Education .",

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AU - Choi, Ye Na

AU - Lee, Sun Kyung

AU - Seo, Tae Woong

AU - Lee, Ji Sun

AU - Yoo, Soon Ji

N1 - Funding Information: We are grateful to Dr. Lee K.H. at Chosun University for the kind gift of VN173 and VC155 constructs used for BiFC assays. This work was supported by the National Research Foundation (NRF) ( 2009-0077619 , 2009-0070405 ). J.S.L. was supported by a Brain Korea 21 Research Fellowship from the Korean Ministry of Education .

PY - 2014/4/18

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N2 - 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.

AB - 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.

KW - Breast cancer

KW - CHIP

KW - Cell migration

KW - Pfn1

KW - Ubiquitin proteasome system

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JF - Biochemical and Biophysical Research Communications

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ER -

C-terminus of Hsc70-interacting protein regulates profilin1 and breast cancer cell migration

Abstract

Bibliographical note

UN SDGs

Keywords

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