Inhibition of G(1) to S phase progression by a novel zinc finger protein P58(TFL) at P-bodies.
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.
Minagawa
Kentaro
K
Department of Medicine, Kobe University Graduate School of Medicine, Japan.
Katayama
Yoshio
Y
Nishikawa
Shinichiro
S
Yamamoto
Katsuya
K
Sada
Akiko
A
Okamura
Atsuo
A
Shimoyama
Manabu
M
Matsui
Toshimitsu
T
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001798:Blood Proteins / Q000096:biosynthesis / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D048708:Cell Growth Processes / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D004247:DNA / Q000096:biosynthesis; D016193:G1 Phase / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D007399:Interphase; D042541:Intracellular Space / Q000378:metabolism; D019169:Jurkat Cells; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D016160:Retinoblastoma Protein / Q000378:metabolism; D016196:S Phase / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers / Q000502:physiology*
D001798:Blood Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D004247:DNA; D053148:Caspase 3