title: Emerging understanding of Bcl-2 biology: Implications for neoplastic progression and treatment.
abstract: Bcl-2, the founding member of a family of apoptotic regulators, was initially identified as the protein product of a gene that is translocated and overexpressed in greater than 85% of follicular lymphomas (FLs). Thirty years later we now understand that anti-apoptotic Bcl-2 family members modulate the intrinsic apoptotic pathway by binding and neutralizing the mitochondrial permeabilizers Bax and Bak as well as a variety of pro-apoptotic proteins, including the cellular stress sensors Bim, Bid, Puma, Bad, Bmf and Noxa. Despite extensive investigation of all of these proteins, important questions remain. For example, how Bax and Bak breach the outer mitochondrial membrane remains poorly understood. Likewise, how the functions of anti-apoptotic Bcl-2 family members such as eponymous Bcl-2 are affected by phosphorylation or cancer-associated mutations has been incompletely defined. Finally, whether Bcl-2 family members can be successfully targeted for therapeutic advantage is only now being investigated in the clinic. Here we review recent advances in understanding Bcl-2 family biology and biochemistry that begin to address these questions.
authors.affiliation: Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Correia
authors.affiliation: Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: X Wei
authors.initials: XW
authors.lastname: Meng
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Nicole D
authors.initials: ND
authors.lastname: Vincelette
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Katherine L B
authors.initials: KL
authors.lastname: Knorr
authors.affiliation: Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Husheng
authors.initials: H
authors.lastname: Ding
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Grzegorz S
authors.initials: GS
authors.lastname: Nowakowski
authors.affiliation: Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: Dai.Haiming@Mayo.edu.
authors.forename: Haiming
authors.initials: H
authors.lastname: Dai
authors.affiliation: Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA; Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: Kaufmann.Scott@Mayo.edu.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D018450:Disease Progression; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2
keywords: Activation-induced cytidine deaminase; Apoptosis; BH3 mimetic; Follicular lymphoma; Mutation
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