Inhibition of G1 to S Phase Progression by a Novel Zinc Finger Protein P58TFL at P-bodies

Abstract

We recently reported the translocation of the immunoglobulin (Ig) light chain kappa locus gene with a possible tumor suppressor gene, TFL, in transformed follicular lymphoma. However, the functional significance in cell transformation remains to be elucidated. Here, we first identified two gene products, P58(TFL) and P36(TFL), derived by alternative splicing. The expression was prominent in normal human lymphocytes but defective in some leukemia/lymphoma cell lines. Overexpression of either protein in a mouse pro-B cell line, Ba/F3, and a human leukemia cell line, Jurkat, inhibited G(1) to S phase progression through suppression of retinoblastoma protein (Rb) phosphorylation. The dominant gene product, P58(TFL), colocalized with mRNA-processing body markers, eukaryotic translation initiation factor 2C and DCP1 decapping-enzyme homolog A, but not with a stress granule maker, T-cell intracellular antigen 1, in the cytoplasm. Taken together with the unique CCCH-type zinc finger motif, the present study suggests that P58(TFL) could play an important role in the regulation of cell growth through posttranscriptional modification of cell cycle regulators, at least partially, upstream of Rb.