Loss of the BH3-only protein Bmf impairs B cell homeostasis and accelerates gamma irradiation-induced thymic lymphoma development

Labi, V; Erlacher, M; Kiessling, S; Manzl, C; Frenzel, A; O&#39;Reilly, L; Strasser, A; Villunger, A

Author(s): Labi, V; Erlacher, M; Kiessling, S; Manzl, C; Frenzel, A; O'Reilly, L; Strasser, A; Villunger, A;
Details: Publication Year 2008-03-17,Volume 205,Issue #3,Page 641-655
Journal Title: JOURNAL OF EXPERIMENTAL MEDICINE
Publication Type: Journal Article
Abstract: Members of the Bcl-2 protein family play crucial roles in the maintenance of tissue homeostasis by regulating apoptosis in response to developmental cues or exogenous stress. Proapoptotic BH3-only members of the Bcl-2 family are essential for initiation of cell death, and they function by activating the proapoptotic Bcl-2 family members Bax and/or Bak, either directly or indirectly through binding to prosurvival Bcl-2 family members. Bax and Bak then elicit the downstream events in apoptosis signaling. Mammals have at least eight BH3-only proteins and they are activated in a stimulus-specific, as well as a cell type-specific, manner. We have generated mice lacking the BH3-only protein Bcl-2-modifying factor (Bmf) to investigate its role in cell death signaling. Our studies reveal that Bmf is dispensable for embryonic development and certain forms of stress-induced apoptosis, including loss of cell attachment (anoikis) or UV irradiation. Remarkably, loss of Bmf protected lymphocytes against apoptosis induced by glucocorticoids or histone deacetylase inhibition. Moreover, bmf(-/-) mice develop a B cell-restricted lymphadenopathy caused by the abnormal resistance of these cells to a range of apoptotic stimuli. Finally, Bmf-deficiency accelerated the development of gamma irradiation-induced thymic lymphomas. Our results demonstrate that Bmf plays a critical role in apoptosis signaling and can function as a tumor suppressor.
Publisher: ROCKEFELLER UNIV PRESS
Keywords: FAMILY-MEMBER BIM; HISTONE DEACETYLASE INHIBITORS; INTESTINAL EPITHELIAL-CELLS; INDUCED APOPTOSIS; DOWN-REGULATION; DEFICIENT MICE; MOTOR COMPLEX; IN-VIVO; BCL-2; DEATH
Publisher's Version: https://doi.org/10.1084/jem.20071658
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2008-03-17 12:00:00