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Molecular and Cellular Biology, April 2006, p. 2924-2935, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.2924-2935.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Novel Role for RbAp48 in Tissue-Specific, Estrogen Deficiency-Dependent Apoptosis in the Exocrine Glands

Naozumi Ishimaru,¹ Rieko Arakaki,¹ Fumie Omotehara,¹ Koichi Yamada,² Kenji Mishima,² Ichiro Saito,² and Yoshio Hayashi^1*

Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3 Kuramotocho, Tokushima 770-8504,¹ Department of Pathology, Tsurumi University School of Dentistry, Tsurumi, Japan²

Received 1 August 2005/ Returned for modification 31 August 2005/ Accepted 20 January 2006

Although tissue-specific apoptosis in the exocrine glands in estrogen-deficient mice may contribute to the development of autoimmune exocrinopathy, the molecular mechanism responsible for tissue-specific apoptosis remains obscure. Here we show that RbAp48 overexpression induces p53-mediated apoptosis in the exocrine glands caused by estrogen deficiency. RbAp48-inducible transfectant results in rapid apoptosis with p53 phosphorylation (Ser9) and -fodrin cleavage. Reducing the expression of RbAp48 through small interfering RNA inhibits the apoptosis. Prominent RbAp48 expression with apoptosis was observed in the exocrine glands of C57BL/6 ovariectomized (OVX) mice but not in OVX estrogen receptor ^–/–, p53^–/–, and E2F-1^–/– mice. Indeed, transgenic expression of the RbAp48 gene induced apoptosis in the exocrine glands but not in other organs. These findings indicate that estrogen deficiency initiates p53-mediated apoptosis in the exocrine gland cells through RbAp48 overexpression and exerts a possible gender-based risk of autoimmune exocrinopathy in postmenopausal women.

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* Corresponding author. Mailing address: Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3 Kuramotocho, Tokushima 770-8504, Japan. Phone: 81 88 633 7327. Fax: 81 88 633 7327. E-mail: hayashi{at}dent.tokushima-u.ac.jp.

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Molecular and Cellular Biology, April 2006, p. 2924-2935, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.2924-2935.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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