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SHP‐1 suppresses cancer cell growth by promoting degradation of JAK kinases
Author(s) -
Wu Chengyu,
Guan Qin,
Wang Yingjian,
Zhao Z. Joe,
Zhou G. Wayne
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10727
Subject(s) - cancer research , jurkat cells , cell growth , kinase , cell culture , mg132 , cancer cell , cancer , biology , proteasome inhibitor , proteasome , microbiology and biotechnology , t cell , immunology , biochemistry , genetics , immune system
SHP ‐ 1 has been proposed to be a tumor suppressor gene for several cancers. The expression of SHP‐1 protein is diminished or abolished in most leukemia and lymphoma cell lines and tissues, and in some non‐hematopoietic cancer cell lines, such as estrogen receptor (ER) negative breast cancer cell lines and some colorectal cancer cell lines. However, we do not know whether the reduced SHP‐1 expression is the cause of cancer diseases or the secondary effect of cancer developments. Here, we first demonstrate that SHP‐1 has general tumor suppressing function in SHP‐1 transfected cell lines. Transfected SHP‐1 inhibits the growth of three lymphoma/leukemia cell lines (Ramos, H9, Jurkat) and one breast cancer cell line (HTB26). We also demonstrate a possible molecular mechanism for the tumor suppressing function of SHP‐1: SHP‐1 inhibits cell growth partly by negative regulation of activated JAK kinase. In addition, we find, for the first time, that SHP‐1 down‐regulates the level of TYK2 kinase in H9 cells and of JAK1 kinase in HTB26 cells, by accelerating their degradation. The SHP‐1 accelerated degradation of JAK1 kinase in HTB26 cells was blocked with the treatment of MG132, a specific inhibitor for proteasome‐mediated proteolysis. Our data suggest a new function of SHP‐1 in the regulation of proteasome‐mediated degradation pathway. © 2003 Wiley‐Liss, Inc.