Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. Sep 1997; 17(9): 5485–5498.
PMCID: PMC232397

FIN13, a novel growth factor-inducible serine-threonine phosphatase which can inhibit cell cycle progression.


We have identified a novel type 2C serine-threonine phosphatase, FIN13, whose expression is induced by fibroblast growth factor 4 and serum in late G1 phase. The protein encoded by FIN13 cDNA includes N- and C-terminal domains with significant homologies to type 2C phosphatases, a domain homologous to collagen, and an acidic domain. FIN13 expression predominates in proliferating tissues. Bacterially expressed FIN13 and FIN13 expressed in mammalian cells exhibit serine-threonine phosphatase activity, which requires Mn2+ and is insensitive to inhibition by okadaic acid. FIN13 is localized in the nuclei of transiently transfected cells. Cotransfection of FIN13-expressing plasmids with a plasmid that expresses the neomycin resistance gene inhibits the growth of drug-resistant colonies in NIH 3T3, HeLa and Rat-1 cells. In transiently transfected cells, FIN13 inhibits DNA synthesis and results in the accumulation of cells in G1 and early S phases. Similarly, the induction of expression of FIN13 under the control of a tetracycline-regulated promoter in NIH 3T3 cells leads to growth inhibition, with accumulation of cells in G1 and early S phases. Thus, overexpression and/or unregulated expression of FIN13 inhibits cell cycle progression, indicating that the physiological role of this phosphatase may be that of regulating the orderly progression of cells through the mitotic cycle by dephosphorylating specific substrates which are important for cell proliferation.

Full Text

The Full Text of this article is available as a PDF (2.2M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Brautigan DL. Protein phosphatases. Recent Prog Horm Res. 1994;49:197–214. [PubMed]
  • Brautigan DL. Flicking the switches: phosphorylation of serine/threonine protein phosphatases. Semin Cancer Biol. 1995 Aug;6(4):211–217. [PubMed]
  • Brondello JM, McKenzie FR, Sun H, Tonks NK, Pouysségur J. Constitutive MAP kinase phosphatase (MKP-1) expression blocks G1 specific gene transcription and S-phase entry in fibroblasts. Oncogene. 1995 May 18;10(10):1895–1904. [PubMed]
  • Chen RH, Sarnecki C, Blenis J. Nuclear localization and regulation of erk- and rsk-encoded protein kinases. Mol Cell Biol. 1992 Mar;12(3):915–927. [PMC free article] [PubMed]
  • Chen X, Ko LJ, Jayaraman L, Prives C. p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev. 1996 Oct 1;10(19):2438–2451. [PubMed]
  • Cohen P, Cohen PT. Protein phosphatases come of age. J Biol Chem. 1989 Dec 25;264(36):21435–21438. [PubMed]
  • Das AK, Helps NR, Cohen PT, Barford D. Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution. EMBO J. 1996 Dec 16;15(24):6798–6809. [PMC free article] [PubMed]
  • Diller L, Kassel J, Nelson CE, Gryka MA, Litwak G, Gebhardt M, Bressac B, Ozturk M, Baker SJ, Vogelstein B, et al. p53 functions as a cell cycle control protein in osteosarcomas. Mol Cell Biol. 1990 Nov;10(11):5772–5781. [PMC free article] [PubMed]
  • Dingwall C, Laskey RA. Nuclear targeting sequences--a consensus? Trends Biochem Sci. 1991 Dec;16(12):478–481. [PubMed]
  • Fantl WJ, Johnson DE, Williams LT. Signalling by receptor tyrosine kinases. Annu Rev Biochem. 1993;62:453–481. [PubMed]
  • Frohman MA, Dush MK, Martin GR. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. [PMC free article] [PubMed]
  • Galaktionov K, Chen X, Beach D. Cdc25 cell-cycle phosphatase as a target of c-myc. Nature. 1996 Aug 8;382(6591):511–517. [PubMed]
  • Givol I, Givol D, Rulong S, Resau J, Tsarfaty I, Hughes SH. Overexpression of human p21waf1/cip1 arrests the growth of chicken embryo fibroblasts transformed by individual oncogenes. Oncogene. 1995 Dec 21;11(12):2609–2618. [PubMed]
  • Gossen M, Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5547–5551. [PMC free article] [PubMed]
  • Gould KL, Nurse P. Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature. 1989 Nov 2;342(6245):39–45. [PubMed]
  • Guthridge M, Bertolini J, Cowling J, Hearn MT. Localization of bFGF mRNA in cyclic rat ovary, diethylstilbesterol primed rat ovary, and cultured rat granulosa cells. Growth Factors. 1992;7(1):15–25. [PubMed]
  • Guthridge MA, Seldin M, Basilico C. Induction of expression of growth-related genes by FGF-4 in mouse fibroblasts. Oncogene. 1996 Mar 21;12(6):1267–1278. [PubMed]
  • Har-el R, Sharma YD, Aguilera A, Ueyama N, Wu JJ, Eyre DR, Juricić L, Chandrasekaran S, Li M, Nah HD, et al. Cloning and developmental expression of the alpha 3 chain of chicken type IX collagen. J Biol Chem. 1992 May 15;267(14):10070–10076. [PubMed]
  • Hunter T. Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell. 1995 Jan 27;80(2):225–236. [PubMed]
  • Kozak M. Structural features in eukaryotic mRNAs that modulate the initiation of translation. J Biol Chem. 1991 Oct 25;266(30):19867–19870. [PubMed]
  • Mann DJ, Campbell DG, McGowan CH, Cohen PT. Mammalian protein serine/threonine phosphatase 2C: cDNA cloning and comparative analysis of amino acid sequences. Biochim Biophys Acta. 1992 Feb 28;1130(1):100–104. [PubMed]
  • Marley AE, Sullivan JE, Carling D, Abbott WM, Smith GJ, Taylor IW, Carey F, Beri RK. Biochemical characterization and deletion analysis of recombinant human protein phosphatase 2C alpha. Biochem J. 1996 Dec 15;320(Pt 3):801–806. [PMC free article] [PubMed]
  • Marshall CJ. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell. 1995 Jan 27;80(2):179–185. [PubMed]
  • Michieli P, Chedid M, Lin D, Pierce JH, Mercer WE, Givol D. Induction of WAF1/CIP1 by a p53-independent pathway. Cancer Res. 1994 Jul 1;54(13):3391–3395. [PubMed]
  • Murray A. Cell cycle checkpoints. Curr Opin Cell Biol. 1994 Dec;6(6):872–876. [PubMed]
  • Noguchi T, Metz R, Chen L, Mattéi MG, Carrasco D, Bravo R. Structure, mapping, and expression of erp, a growth factor-inducible gene encoding a nontransmembrane protein tyrosine phosphatase, and effect of ERP on cell growth. Mol Cell Biol. 1993 Sep;13(9):5195–5205. [PMC free article] [PubMed]
  • Reynisdóttir I, Polyak K, Iavarone A, Massagué J. Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-beta. Genes Dev. 1995 Aug 1;9(15):1831–1845. [PubMed]
  • Saus J, Quinones S, MacKrell A, Blumberg B, Muthukumaran G, Pihlajaniemi T, Kurkinen M. The complete primary structure of mouse alpha 2(IV) collagen. Alignment with mouse alpha 1(IV) collagen. J Biol Chem. 1989 Apr 15;264(11):6318–6324. [PubMed]
  • Scherens B, el Bakkoury M, Vierendeels F, Dubois E, Messenguy F. Sequencing and functional analysis of a 32,560 bp segment on the left arm of yeast chromosome II. Identification of 26 open reading frames, including the KIP1 and SEC17 genes. Yeast. 1993 Dec;9(12):1355–1371. [PubMed]
  • Schlessinger J, Ullrich A. Growth factor signaling by receptor tyrosine kinases. Neuron. 1992 Sep;9(3):383–391. [PubMed]
  • Sherr CJ. G1 phase progression: cycling on cue. Cell. 1994 Nov 18;79(4):551–555. [PubMed]
  • Sun H, Charles CH, Lau LF, Tonks NK. MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Cell. 1993 Nov 5;75(3):487–493. [PubMed]
  • Terasawa T, Kobayashi T, Murakami T, Ohnishi M, Kato S, Tanaka O, Kondo H, Yamamoto H, Takeuchi T, Tamura S. Molecular cloning of a novel isotype of Mg(2+)-dependent protein phosphatase beta (type 2C beta) enriched in brain and heart. Arch Biochem Biophys. 1993 Dec;307(2):342–349. [PubMed]
  • Wenk J, Mieskes G. Cytosolic and nuclear localization of protein phosphatase 2C beta 1 in COS and BHK cells. Eur J Cell Biol. 1995 Dec;68(4):377–386. [PubMed]
  • Wenk J, Trompeter HI, Pettrich KG, Cohen PT, Campbell DG, Mieskes G. Molecular cloning and primary structure of a protein phosphatase 2C isoform. FEBS Lett. 1992 Feb 3;297(1-2):135–138. [PubMed]
  • Wilson R, Ainscough R, Anderson K, Baynes C, Berks M, Bonfield J, Burton J, Connell M, Copsey T, Cooper J, et al. 2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans. Nature. 1994 Mar 3;368(6466):32–38. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene links
  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...