Anp32e (Cpd1) and related protein phosphatase 2 inhibitors

Mouse Anp32e (Acidic leucine-rich nuclear phosphoprotein 32 family, member e: NM_023210, P97822, formerly Cpd1), a protein identified in postnatal cerebellum by differential display, belongs to the superfamily of leucine rich repeat (LRR) proteins and to the Acidic Nuclear Phosphoprotein 32 (ANP32) family of protein phosphatase 2 (PPP2, formerly PP2A) inhibitors. Two families of PPP2 inhibitor proteins have been described, ANP32 and SET, represented by the human proteins ANP32A (NM_006305, formerly LANP, PP32, I1PPP2, PHAPI, MAPM, mapmodulin) and SET (NM_003011, formerly PHAPII, 2PPP2, I2PPP2, TAF-1BETA). Besides their common PPP2 inhibitor activity, described several years ago, these nucleo-cytoplasmic shuttling phosphoproteins have additional and very important functions recently reported. In HeLa cells, ANP32A, SET (isoforms A and B) and ANP32B (APRIL), form a multi-subunit heterocomplex with ELAVL1 (NM_001419, formerly HuR), a protein that stabilizes short-lived mRNAs containing AU-rich elements (AREs). A similar heterocomplex, formed by SET (A and B) and ANP32A as major subunits, possess histone acetyltransferase inhibitory activity (INHAT), and have a role in chromatin remodeling and transcriptional regulation (histone code). The possible roles of these multifunctional proteins are discussed here, with emphasis on mouse Anp32e and the cerebellar tissue.