Kindlin-3 interacts with the ribosome and regulates c-Myc expression required for proliferation of chronic myeloid leukemia cells

• Main Authors: 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
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2016
• Subjects: Extracellular matrix; Integrins
• Online Access: https://hdl.handle.net/10356/81542; http://hdl.handle.net/10220/39588
• Institution: Nanyang Technological University

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.