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MAGE-A, mMage-b, andMAGE-C Proteins FormComplexes with KAP1and Suppressp53-DependentApoptosis inMAGE-Positive CellLines Bing YangSean M. O’HerrinJianqiang Wu2007 год

MAGE-A, mMage-b, and MAGE-C Proteins Form Complexes with KAP1 and Suppress p53-Dependent Apoptosis in MAGE-Positive Cell Lines
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Аннотация: Abstract The MAGE-A, MAGE-B, and MAGE-C protein families comprise the class-I MAGE/cancer testes antigens, a group of highly homologous proteins whose expression is suppressed in all normal tissues except developing sperm. Aberrant expression of class I MAGE proteins occurs in melanomas and many other malignancies, and MAGE proteins have long been recognized as tumor-specific targets; however, their functions have largely been unknown. Here, we show that suppression of class I MAGE proteins induces apoptosis in the Hs-294T, A375, and S91 MAGE-positive melanoma cell lines and that members of all three families of MAGE class I proteins form complexes with KAP1, a scaffolding protein that is known as a corepressor of p53 expression and function. In addition to inducing apoptosis, MAGE suppression decreases KAP1 complexing with p53, increases immunoreactive and acetylated p53, and activates a p53 responsive reporter gene. Suppression of class I MAGE proteins also induces apoptosis in MAGE-A–positive, p53wt/wt parental HCT 116 colon cancer cells but not in a MAGE-A–positive HCT 116 p53−/− variant, indicating that MAGE suppression of apoptosis requires p53. Finally, treatment with MAGE-specific small interfering RNA suppresses S91 melanoma growth in vivo, in syngenic DBA2 mice. Thus, class I MAGE protein expression may suppress apoptosis by suppressing p53 and may actively contribute to the development of malignancies and by promoting tumor survival. Because the expression of class I MAGE proteins is limited in normal tissues, inhibition of MAGE antigen expression or function represents a novel and specific treatment for melanoma and diverse malignancies. [Cancer Res 2007;67(20):9954–62]
Год издания: 2007
Авторы: Bing Yang, Sean M. O’Herrin, Jianqiang Wu, Shannon Reagan‐Shaw, Yongsheng Ma, Kumar M. R. Bhat, Claudia Gravekamp, Vijayasaradhi Setaluri, Noël R. Peters, F. Michael Hoffmann, Hongzhuang Peng, Alexey V. Ivanov, Andrew J.G. Simpson, B. Jack Longley
Издательство: American Association for Cancer Research
Источник: Cancer Research
Ключевые слова: Immunotherapy and Immune Responses, RNA Interference and Gene Delivery, Renal and related cancers
Другие ссылки: Cancer Research (HTML)
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