Fan Z, Zhang H, Zhang Q
National Laboratory of Biomacromolecules and Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Cell Death Differ. 2006 Sep;13(9):1485-94. doi: 10.1038/sj.cdd.4401825. Epub 2005 Dec 9.
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.
pp32属于富含亮氨酸的酸性核蛋白家族，该家族在包括染色质重塑、转录、RNA转运、转化和细胞凋亡调控在内的许多细胞过程中发挥重要作用。pp32被描述为一种新的肿瘤抑制因子。目前尚不清楚pp32在肿瘤抑制中是如何发挥作用的。我们发现，在人Jurkat T细胞中过表达pp32会抑制细胞生长，而使pp32沉默则会促进细胞生长。我们首先表明，组蛋白H3的高度乙酰化和高度磷酸化是T细胞激活所必需的。在T细胞激活过程中，组蛋白H3的磷酸化先于乙酰化。pp32特异性结合组蛋白H3并阻断其乙酰化和磷酸化。pp32直接启动半胱天冬酶活性，还促进颗粒酶A介导的非半胱天冬酶依赖性细胞死亡。综上所述，pp32通过抑制转录和触发细胞凋亡发挥抑制作用。
