A nuclear factor containing the leucine-rich repeats expressed in murine cerebellar neurons.

Abstract

A nuclear protein, termed leucine-rich acidic nuclear protein (LANP), has been Isolated from among rat cerebellar proteins whose expression was transiently increased during an early stage ofpostnatal development. The amino acid sequence, deduced from its cDNA, showed that LANP contains 247 amino acids consisting of two distinct structural doains: the N-terminal domain characterized by "leucine-rich repeat," which is found in many eukaryotic proteins and which potentially functions in mediating protein-protein interactions, and the C-terminal domain characterized by a cduster of acidic amino acids with a putative nuclear loalization signal. Immunohistochemical study using an antibody against LANP revealed that the protein is localized mainly in nuclei of Purkinje cells. In the rat cerebellum on postnatal day 7, LANP mRNA was expressed moderately in the external granule and Purklije cells and weakly in the internal granule cells. The expression in these cells, especially in Purkinje cells, increased in the second postnatal week and thereafter decreased to an adult level. The structural characteristics, localization, and the stage-and cell type-specific expression suggest a potential role of LANP in a signal transduction pathway that directs differentiation of cerebellar neurons.Morphogenesis of the mammalian central nervous system is a dynamic cellular process that includes neuronal proliferation, differentiation and migration, synaptogenesis, and synaptic rearrangement (1, 2). Several lines of evidence suggest that these morphogenetic changes result from a series of molecular events programed at a transcriptional or posttranscriptional level, such as the control of the expression of proteins during development or posttranslational modifications of expressed proteins frequently by reversible phosphorylation (3-5). Thus, one of the crucial approaches to study the morphogenetic process at the molecular level is to explore molecules that play pivotal roles in the development of the nervous system.Murine cerebellum is suitable for such an experimental analysis because (i) the cerebellum has a highly ordered geometric organization composed of a relatively small number of neuronal populations and much information has been accumulated on the development of its neuronal circuits (1, 2); (ii) mutant animals with defects of the cerebellum have become available, which enables investigation of relationships among biochemical, morphological, and physiological changes; and (iii) most of the morphogenetic changes in the murine cerebellar cortex are the early postnatal events (1, 2). On the basis of protein maps obtained by two-dimensional (2D) HPLC (6) and 2D electrophoresis (2D PAGE) we screened several hundred proteins with respect to their temporal profiles of expression during the development and identified a group of proteins whose expression transiently reached a maximum level within the first 3 postnatal weeks, the period that is most critical for murine cerebellar morphogenesis. One of those proteins, termed "V-1...

pp32, an INHAT component, is a transcription machinery recruiter for maximal induction of IFN-stimulated genes

“…1C) and that the pp32-STAT2-STAT1 complex is found only in the nucleus (Fig. 1B), in agreement with reports that pp32 is localized in the nucleus and type I IFN stimulates the nuclear translocation of STAT2 and STAT1 (Matilla et al, 1997; 897 pp32 regulates ISG transcription Matsuoka et al, 1994;Schindler et al, 1992). Our results suggest that pp32 regulates the formation of the transcriptional complex in the nucleus.…”

“…1B). pp32 was localized in the nucleus in good agreement with previous reports (Matilla et al, 1997;Matsuoka et al, 1994), and the intracellular distribution pattern of pp32 was not altered by IFN stimulation (Fig. 1B).…”

“…pp32, alternatively designated Anp32a/Lanp/PHAPI, is a member of the Anp32 family, which encode leucine-rich repeat (LRR) domains and an acidic domain in their N-terminal and C-terminal regions, respectively (Matsuoka et al, 1994). pp32 is a multifunctional protein that is implicated in mRNA transport, the cell cycle, apoptosis, cellular morphology, and multiple cellular pathways regulated by protein phosphatase 2A (Matilla and Radrizzani, 2005).…”

Isolation and functional identification of a novel human hepatic growth factor: Hepatopoietin Cn

“…LANP proteins typically contain leucine-rich repeat motifs followed by an acidic carboxyterminal tail and are heat-stable, and are involved in a variety of biological pathways, including signaling, protein degradation, cytoskeletal dynamics, and morphogenesis, presumably based on the ability of the leucine-rich repeat (LRR) domains to serve as adapter sites for protein-protein interactions. 23,24 Previous biochemical studies suggested that human LANP (pp32/I 1 PP2A/ mapmodulin/HPPCn) has been implicated in a number of cellular processes in both nucleus and cytoplasm, including proliferation, 24 differentiation, 23 caspase-dependent and caspase-independent apoptosis, 25 suppression of transformation in vivo, 26 inhibition of protein phosphatase 2A, 27 regulation of mRNA trafficking and stability in association with HuR, 28 and inhibition of acetyltransferases as part of the INHAT complex. 29 In this report, we found that rhHPPCn may stimulate the DNA synthesis and proliferation of hepatocytes and hepatoma cell lines and activate kinase pathways including SPK, ERK1/2, and Stat3.…”

Highly Acidic C-Terminal Domain of pp32 Is Required for the Interaction with Histone Chaperone, TAF-Ibeta

“…9) The other INHAT subunit, pp32 belongs to a family of acidic leucine-rich nuclear proteins that includes April, LANP, and PHAP1. 10,11) LANP was shown to associate with ataxin-1 and pp32 has also been reported to suppress cell transformation induced by oncogenes, including Ras and Myc. 12,13) Like TAF-Ibeta and TAF-Ialpha, pp32 also has Cterminal acidic tail, indicating an evolutionary conserved role for this domain in the function of these proteins.…”