Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells
Kindlins are FERM-containing cytoplasmic proteins that regulate integrin-mediated cell-cell and cell-extracellular matrix (ECM) attachments. Kindlin-3 is expressed in hematopoietic cells, platelets, and endothelial cells. Studies have shown that kindlin-3 stabilizes cell adhesion mediated by ß1, ß2,...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2016
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/81542 http://hdl.handle.net/10220/39588 |
| _version_ | 1826129295960965120 |
|---|---|
| author | Qu, Jing Ero, Rya Feng, Chen Ong, Li-Teng Tan, Hui-Foon Lee, Hui-Shan Ismail, Muhammad HB Bu, Wen-Ting Nama, Srikanth Sampath, Prabha Gao, Yong-Gui Tan, Suet-Mien |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Qu, Jing Ero, Rya Feng, Chen Ong, Li-Teng Tan, Hui-Foon Lee, Hui-Shan Ismail, Muhammad HB Bu, Wen-Ting Nama, Srikanth Sampath, Prabha Gao, Yong-Gui Tan, Suet-Mien |
| author_sort | Qu, Jing |
| collection | NTU |
| description | Kindlins are FERM-containing cytoplasmic proteins that regulate integrin-mediated cell-cell and cell-extracellular matrix (ECM) attachments. Kindlin-3 is expressed in hematopoietic cells, platelets, and endothelial cells. Studies have shown that kindlin-3 stabilizes cell adhesion mediated by ß1, ß2, and ß3 integrins. Apart from integrin cytoplasmic tails, kindlins are known to interact with other cytoplasmic proteins. Here we demonstrate that kindlin-3 can associate with ribosome via the receptor for activated-C kinase 1 (RACK1) scaffold protein based on immunoprecipitation, ribosome binding, and proximity ligation assays. We show that kindlin-3 regulates c-Myc protein expression in the human chronic myeloid leukemia cell line K562. Cell proliferation was reduced following siRNA reduction of kindlin-3 expression and a significant reduction in tumor mass was observed in xenograft experiments. Mechanistically, kindlin-3 is involved in integrin α5ß1-Akt-mTOR-p70S6K signaling; however, its regulation of c-Myc protein expression could be independent of this signaling axis. |
| first_indexed | 2024-10-01T07:38:18Z |
| format | Journal Article |
| id | ntu-10356/81542 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:38:18Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | ntu-10356/815422023-02-28T16:59:27Z Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells Qu, Jing Ero, Rya Feng, Chen Ong, Li-Teng Tan, Hui-Foon Lee, Hui-Shan Ismail, Muhammad HB Bu, Wen-Ting Nama, Srikanth Sampath, Prabha Gao, Yong-Gui Tan, Suet-Mien School of Biological Sciences Extracellular matrix; Integrins Kindlins are FERM-containing cytoplasmic proteins that regulate integrin-mediated cell-cell and cell-extracellular matrix (ECM) attachments. Kindlin-3 is expressed in hematopoietic cells, platelets, and endothelial cells. Studies have shown that kindlin-3 stabilizes cell adhesion mediated by ß1, ß2, and ß3 integrins. Apart from integrin cytoplasmic tails, kindlins are known to interact with other cytoplasmic proteins. Here we demonstrate that kindlin-3 can associate with ribosome via the receptor for activated-C kinase 1 (RACK1) scaffold protein based on immunoprecipitation, ribosome binding, and proximity ligation assays. We show that kindlin-3 regulates c-Myc protein expression in the human chronic myeloid leukemia cell line K562. Cell proliferation was reduced following siRNA reduction of kindlin-3 expression and a significant reduction in tumor mass was observed in xenograft experiments. Mechanistically, kindlin-3 is involved in integrin α5ß1-Akt-mTOR-p70S6K signaling; however, its regulation of c-Myc protein expression could be independent of this signaling axis. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Published version 2016-01-06T06:08:00Z 2019-12-06T14:33:19Z 2016-01-06T06:08:00Z 2019-12-06T14:33:19Z 2015 Journal Article Qu, J., Ero, R., Feng, C., Ong, L.-T., Tan, H.-F., Lee, H.-S., et al. (2015). Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells. Scientific Reports, 5, 18491-. 2045-2322 https://hdl.handle.net/10356/81542 http://hdl.handle.net/10220/39588 10.1038/srep18491 26677948 en Scientific Reports This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ 16 p. application/pdf |
| spellingShingle | Extracellular matrix; Integrins Qu, Jing Ero, Rya Feng, Chen Ong, Li-Teng Tan, Hui-Foon Lee, Hui-Shan Ismail, Muhammad HB Bu, Wen-Ting Nama, Srikanth Sampath, Prabha Gao, Yong-Gui Tan, Suet-Mien Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells |
| title | Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells |
| title_full | Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells |
| title_fullStr | Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells |
| title_full_unstemmed | Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells |
| title_short | Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells |
| title_sort | kindlin 3 interacts with the ribosome and regulates c myc expression required for proliferation of chronic myeloid leukemia cells |
| topic | Extracellular matrix; Integrins |
| url | https://hdl.handle.net/10356/81542 http://hdl.handle.net/10220/39588 |
| work_keys_str_mv | AT qujing kindlin3interactswiththeribosomeandregulatescmycexpressionrequiredforproliferationofchronicmyeloidleukemiacells AT erorya kindlin3interactswiththeribosomeandregulatescmycexpressionrequiredforproliferationofchronicmyeloidleukemiacells AT fengchen kindlin3interactswiththeribosomeandregulatescmycexpressionrequiredforproliferationofchronicmyeloidleukemiacells AT ongliteng kindlin3interactswiththeribosomeandregulatescmycexpressionrequiredforproliferationofchronicmyeloidleukemiacells AT tanhuifoon kindlin3interactswiththeribosomeandregulatescmycexpressionrequiredforproliferationofchronicmyeloidleukemiacells AT leehuishan kindlin3interactswiththeribosomeandregulatescmycexpressionrequiredforproliferationofchronicmyeloidleukemiacells AT ismailmuhammadhb kindlin3interactswiththeribosomeandregulatescmycexpressionrequiredforproliferationofchronicmyeloidleukemiacells AT buwenting kindlin3interactswiththeribosomeandregulatescmycexpressionrequiredforproliferationofchronicmyeloidleukemiacells AT namasrikanth kindlin3interactswiththeribosomeandregulatescmycexpressionrequiredforproliferationofchronicmyeloidleukemiacells AT sampathprabha kindlin3interactswiththeribosomeandregulatescmycexpressionrequiredforproliferationofchronicmyeloidleukemiacells AT gaoyonggui kindlin3interactswiththeribosomeandregulatescmycexpressionrequiredforproliferationofchronicmyeloidleukemiacells AT tansuetmien kindlin3interactswiththeribosomeandregulatescmycexpressionrequiredforproliferationofchronicmyeloidleukemiacells |