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P53‐dependent and ‐independent components of IL‐2 mediated radioprotection in IL‐2 dependent T cell lines
Author(s) -
Kibe Ryoko,
Zvonic Sanjin,
Iwakuma Tomoo,
Durum Scott K,
Cui Yan
Publication year - 2008
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.22.1_supplement.1070.31
Subject(s) - apoptosis , microbiology and biotechnology , cell cycle , cell cycle checkpoint , protein kinase b , haematopoiesis , dna damage , cell culture , dna repair , chemistry , cancer research , biology , signal transduction , dna , stem cell , genetics
Cytokines are crucial growth factors for the survival, proliferation and differentiation of hematopoictic cells. Previous studies have shown that many cytokines are radioprotective, i.e. able to rescue hematopoietic cells from radiation‐induced apoptosis. The radioprotective role of IL‐2 in IL‐2 dependent T cells and its molecular mechanism has not been well defined. We hypothesize that IL‐2 protects T cells from radiation‐induced apoptosis via up‐regulating antiapoptotic molecules and enhancing DNA repairs. It is well known that upon radiation induced double strand DNA break, cells immediately activate DNA repair machinery and initiate cell cycle arrest. Using IL‐2 dependent p53‐sufficient HT‐2 T cell line and p53‐deficient D1 cell line, we show that IL‐2 protects them from radiation‐induced apoptosis through up‐regulating antiapoptotic molecules and inducing G2 cell cycle arrest via Akt pathway. Although Akt mediated cell cycle arrest may occur independent of p53, it appears to be crucial for p53‐dependent radioprotection as inhibition of Akt activity delays successful repair of damaged DNA, which results in radiation‐induced apoptosis. Therefore, both p53‐dependent and ‐independent pathways are important for IL‐2 mediated radioprotection. This study is supported by NIH grants to YC (CA112065 and P20RR021970)