Activation/Division of Lymphocytes Results in Increased Levels of Cytoplasmic Activation/Proliferation-Associated Protein-1: Prototype of a New Family of Proteins

Abstract

We purified from activated T lymphocytes a novel, highly conserved, 116-kDa, intracellular protein that occurred at high levels in the large, dividing cells of the thymus, was up-regulated when resting T or B lymphocytes or hemopoietic progenitors were activated, and was down-regulated when a monocytic leukemia, M1, was induced to differentiate. Expression of the protein was highest in the thymus and spleen and lowest in tissues with a low proportion of dividing cells such as kidney or muscle, although expression was high in the brain. The protein was localized to the cytosol and was phosphorylated, which is consistent with a previous report that the Xenopus laevis ortholog was phosphorylated by a mitotically activated kinase (1 ). The cDNA was previously mischaracterized as encoding p137, a 137-kDa GPI-linked membrane protein (2 ). We propose that the authentic protein encoded by this cDNA be called cytoplasmic activation/proliferation-associated protein-1 (caprin-1), and show that it is the prototype of a novel family of proteins characterized by two novel protein domains, termed homology regions-1 and -2 (HR-1, HR-2). Although we have found evidence for caprins only in urochordates and vertebrates, two insect proteins exhibit well-conserved HR-1 domains. The HR-1 and HR-2 domains have no known function, although the HR-1 of caprin-1 appeared necessary for formation of multimeric complexes of caprin-1. Overexpression of a fusion protein of enhanced green fluorescent protein and caprin-1 induced a specific, dose-dependent suppression of the proliferation of NIH-3T3 cells, consistent with the notion that caprin-1 plays a role in cellular activation or proliferation.

An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63

“…Interestingly, Caprin-1 is a conserved protein exhibiting RNA binding protein properties (Grill et al, 2004). Caprin-1 is expressed in most tissue types.…”

“…Caprin-1 is expressed in most tissue types. Its expression is increased on entry into cell cycle and decreased on cell division completion (Grill et al, 2004). Wang et al, showed that the absence of Caprin-1 retards cell phase progression from G1 to S and defined Caprin-1 as an essential factor in normal cell proliferation (Wang et al, 2005).…”

“…The role of Caprin-1 direct binding to c-Myc and Cyclin-D2 RNA transcripts is unknown, this binding may promote or repress translation, determine stability, localization and/or associated proteins (Palacios and Johnston, 2001). It is proposed that Caprin-1, through binding of c-Myc and Cyclin-D2 mRNA, is involved in G1/S transition regulation (Grill et al, 2004). In cDNA expression screening, we determined a possible Caprin-1 modification in the presence of active DNA damage responses.…”

Bacterial expression and preliminary crystallographic studies of a 149-residue fragment of human Caprin-1

“…Firstly, Caprin-1 plays an essential role in cellular proliferation. High levels of Caprin-1 have been observed in proliferating T or B lymphocytes and hemopoietic progenitors (Grill et al, 2004). At the tissue level, Caprin-1 is highly expressed in the thymus and the spleen and its level is lowest in tissues with a low proportion of dividing cells (such as kidney or muscle).…”

“…These two proteins contain two homologous regions (HR1 and HR2; Grill et al, 2004;Shiina et al, 2005; Fig. 1).…”