The invariant chain CD74 protein is a cell surface binding partner of TIMP‐1 in breast cancer cells
Tissue inhibitor of metalloproteinases‐1 (TIMP‐1) regulates the proteolytic activity of matrix metalloproteinases (MMPs), playing an important role in the homeostasis of the extracellular matrix. Beyond its well‐known role in tissue maintenance, TIMP‐1 has been associated with multiple MMP‐independe...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-08-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13436 |
| _version_ | 1827878098109988864 |
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| author | Mikkel Høeberg Julie Boertmann Noer Mette Vixø Vistesen Annette Bartels Esben Matzen Bech Sune Boris Nygård Ulrik Lademann Jan Stenvang Siqi Liu Anja Thoe Fuglsang Nils Brünner José Manuel Afonso Moreira |
| author_facet | Mikkel Høeberg Julie Boertmann Noer Mette Vixø Vistesen Annette Bartels Esben Matzen Bech Sune Boris Nygård Ulrik Lademann Jan Stenvang Siqi Liu Anja Thoe Fuglsang Nils Brünner José Manuel Afonso Moreira |
| author_sort | Mikkel Høeberg |
| collection | DOAJ |
| description | Tissue inhibitor of metalloproteinases‐1 (TIMP‐1) regulates the proteolytic activity of matrix metalloproteinases (MMPs), playing an important role in the homeostasis of the extracellular matrix. Beyond its well‐known role in tissue maintenance, TIMP‐1 has been associated with multiple MMP‐independent cytokine‐like functions. The protein structure of TIMP‐1, with two distinct domains, one interacting with MMPs and another able to bind multiple partners, provides a rationale for this multifunctionality. The identification of CD63 as a cell surface receptor for TIMP‐1, able to mediate intracellular signaling through the Erk/MAPK axis, provided a molecular basis for the role of TIMP‐1 in cellular signaling. However, several lines of evidence suggest that TIMP‐1 may be able to associate with many interaction partners, thus attaining multiple functions. To enable the identification of previously unknown interaction partners that may underpin the core cellular functions of TIMP‐1, known as well as unknown, we performed a yeast two‐hybrid screening using a mammary gland complementary DNA (cDNA) library. We report here the identification of multiple interactors, including MHC class II‐associated invariant chain γ (CD74). We verified that CD74 interacts with TIMP‐1 in breast cancer cells and that this interaction contributes to cellular internalization of TIMP‐1 and mediates intracellular signaling through the Akt signaling axis in breast cancer cells. These data provide new insights into the complex nature of the functions of TIMP‐1 and their potential mechanistic basis. |
| first_indexed | 2024-03-12T17:46:29Z |
| format | Article |
| id | doaj.art-514da4a7f4ac4728b3148bc37682ce11 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-03-12T17:46:29Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-514da4a7f4ac4728b3148bc37682ce112023-08-03T16:44:14ZengWileyMolecular Oncology1574-78911878-02612023-08-011781595161210.1002/1878-0261.13436The invariant chain CD74 protein is a cell surface binding partner of TIMP‐1 in breast cancer cellsMikkel Høeberg0Julie Boertmann Noer1Mette Vixø Vistesen2Annette Bartels3Esben Matzen Bech4Sune Boris Nygård5Ulrik Lademann6Jan Stenvang7Siqi Liu8Anja Thoe Fuglsang9Nils Brünner10José Manuel Afonso Moreira11Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen DenmarkDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen DenmarkDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen DenmarkDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen DenmarkTransport Biology section, Department of Plant and Environmental Sciences University of Copenhagen DenmarkDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen DenmarkDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen DenmarkDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen DenmarkBeijing Institute of Genomics Chinese Academy of Sciences Beijing ChinaTransport Biology section, Department of Plant and Environmental Sciences University of Copenhagen DenmarkDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen DenmarkDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen DenmarkTissue inhibitor of metalloproteinases‐1 (TIMP‐1) regulates the proteolytic activity of matrix metalloproteinases (MMPs), playing an important role in the homeostasis of the extracellular matrix. Beyond its well‐known role in tissue maintenance, TIMP‐1 has been associated with multiple MMP‐independent cytokine‐like functions. The protein structure of TIMP‐1, with two distinct domains, one interacting with MMPs and another able to bind multiple partners, provides a rationale for this multifunctionality. The identification of CD63 as a cell surface receptor for TIMP‐1, able to mediate intracellular signaling through the Erk/MAPK axis, provided a molecular basis for the role of TIMP‐1 in cellular signaling. However, several lines of evidence suggest that TIMP‐1 may be able to associate with many interaction partners, thus attaining multiple functions. To enable the identification of previously unknown interaction partners that may underpin the core cellular functions of TIMP‐1, known as well as unknown, we performed a yeast two‐hybrid screening using a mammary gland complementary DNA (cDNA) library. We report here the identification of multiple interactors, including MHC class II‐associated invariant chain γ (CD74). We verified that CD74 interacts with TIMP‐1 in breast cancer cells and that this interaction contributes to cellular internalization of TIMP‐1 and mediates intracellular signaling through the Akt signaling axis in breast cancer cells. These data provide new insights into the complex nature of the functions of TIMP‐1 and their potential mechanistic basis.https://doi.org/10.1002/1878-0261.13436breast cancercell signalinginvariant chain (CD74)receptorTIMP‐1 interaction |
| spellingShingle | Mikkel Høeberg Julie Boertmann Noer Mette Vixø Vistesen Annette Bartels Esben Matzen Bech Sune Boris Nygård Ulrik Lademann Jan Stenvang Siqi Liu Anja Thoe Fuglsang Nils Brünner José Manuel Afonso Moreira The invariant chain CD74 protein is a cell surface binding partner of TIMP‐1 in breast cancer cells Molecular Oncology breast cancer cell signaling invariant chain (CD74) receptor TIMP‐1 interaction |
| title | The invariant chain CD74 protein is a cell surface binding partner of TIMP‐1 in breast cancer cells |
| title_full | The invariant chain CD74 protein is a cell surface binding partner of TIMP‐1 in breast cancer cells |
| title_fullStr | The invariant chain CD74 protein is a cell surface binding partner of TIMP‐1 in breast cancer cells |
| title_full_unstemmed | The invariant chain CD74 protein is a cell surface binding partner of TIMP‐1 in breast cancer cells |
| title_short | The invariant chain CD74 protein is a cell surface binding partner of TIMP‐1 in breast cancer cells |
| title_sort | invariant chain cd74 protein is a cell surface binding partner of timp 1 in breast cancer cells |
| topic | breast cancer cell signaling invariant chain (CD74) receptor TIMP‐1 interaction |
| url | https://doi.org/10.1002/1878-0261.13436 |
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