title: Bim: guardian of tissue homeostasis and critical regulator of the immune system, tumorigenesis and bone biology.
abstract: One of the most important roles of apoptosis is the maintenance of tissue homeostasis. Impairment of apoptosis leads to a number of pathological conditions. In response to apoptotic signals, various proteins are activated in a pathway and signal-specific manner. Recently, the pro-apoptotic molecule Bim has attracted increasing attention as a pivotal regulator of tissue homeostasis. The Bim expression level is strictly controlled in both transcriptional and post-transcriptional levels. This control is dependent on cell, tissue and apoptotic stimuli. The phenotype of Bim-deficient mice is a systemic lupus erythematosus-like autoimmune disease with an abnormal accumulation of hematopoietic cells. Bim is thus a critical regulator of hematopoietic cells and immune system. Further studies have revealed the critical roles of Bim in various normal and pathological conditions, including bone homeostasis and tumorigenesis. The current understanding of Bim signaling and roles in the maintenance of tissue homeostasis is reviewed in this paper, focusing on the immune system, bone biology and tumorigenesis to illustrate the diversified role of Bim.
authors.affiliation: Department of Orthopaedic Surgery, Saitama Medical Center, Jichi Medical University, Omiya-ku, Saitama, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Akiyama
authors.forename: Sakae
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000502:physiology*; D001327:Autoimmune Diseases; D000072224:Bcl-2-Like Protein 11; D001842:Bone and Bones / Q000502:physiology*; D002460:Cell Line; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007107:Immune System / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000503:physiopathology; D008565:Membrane Proteins / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D008954:Models, Biological; D009369:Neoplasms / Q000503:physiopathology*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins