Tumor suppressor pp32 represses cell growth through inhibition of transcription by blocking acetylation and phosphorylation of histone H3 and initiating its proapoptotic activity.
pp32 belongs to a family of leucine-rich acidic nuclear proteins, which play important roles in many cellular processes including regulation of chromatin remodeling, transcription, RNA transport, transformation and apoptosis. pp32 is described as a new tumor suppressor. It is unknown as to how pp32 works in tumor suppression. We found that overexpression of pp32 in human Jurkat T cells inhibits cell growth, and silenced pp32 promotes growth. We first showed that hyperacetylation and hyperphosphorylation of histone H3 are required for T-cell activation. Phosphorylation of histone H3 precedes acetylation during T-cell activation. pp32 specifically binds to histone H3 and blocks its acetylation and phosphorylation. pp32 directly initiates caspase activity and also promotes granzyme A-mediated caspase-independent cell death. Taken together, pp32 plays a repressive role by inhibiting transcription and triggering apoptosis.
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National Laboratory of Biomacromolecules and Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. fanz@moon.ibp.ac.cn
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D000107:Acetylation; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation; D004789:Enzyme Activation; D053804:Granzymes / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000502:physiology*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000502:physiology; D010766:Phosphorylation; D014158:Transcription, Genetic
D006657:Histones; D007376:Interleukin-2; D009687:Nuclear Proteins; D010750:Phosphoproteins; D053804:Granzymes; D053148:Caspase 3; D053453:Caspase 9