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Stabilization of OCT4 by hypoxia mimetics, nickel and cobalt
Author(s) -
Yao Yixin,
Dai Wei
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.553.3
Subject(s) - klf4 , homeobox protein nanog , stem cell , induced pluripotent stem cell , reprogramming , microbiology and biotechnology , chemistry , biology , cancer research , embryonic stem cell , cell , biochemistry , gene
Stem cell research can lead to the development of treatments for a wide range of diseases including diabetes, heart disease, neurodegenerative diseases, aging, and cancer. OCT4 is an essential gene for the maintenance and expansion of stem cells. OCT4 also plays a primary role in reprogramming of somatic cells into induced pluripotent stem (iPS) cells. Given that hypoxia can enhance the generation of iPS cells, we examined expression of several stem cell factors in Tera‐1 cells that were exposed to nickel or cobalt, two well‐known hypoxia mimetic agents. Nickel treatment induced a concentration‐dependent increase in expression of OCT4 and HIF‐1a, but not SOX‐2, NANOG, c‐Myc and KLF4. Nickel‐induced OCT4 expression was due primarily to protein stabilization because MG132 alone or in combination with nickel increased OCT4 expression and because nickel did not significantly modulate the steady‐state mRNA level of OCT4. Nickel also stabilized OCT4 when new protein synthesis was inhibited by the treatment with cycloheximide. Moreover, cobalt treatment induced expression of OCT4 as well. Combined, these results indicate that enhanced expression of OCT4 under the hypoxic condition is mediated at least in part through protein stabilization. Our study also implicates that exposure to nickel and/or cobalt may affect stem cell proliferation and differentiation in vivo.