Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Induction of Cellular Senescence: Role of Mitogen-Activated Protein Kinase-Interacting Kinase 1

  • Chapter
  • First Online:
Tumor Dormancy, Quiescence, and Senescence, Volume 2

Part of the book series: Tumor Dormancy and Cellular Quiescence and Senescence ((DOQU,volume 2))

  • 1459 Accesses

Abstract

Heterogeneous nuclear ribonucleoprotein (hnRNP) family members are the most abundant components of messenger ribonucleoprotein complexes (mRNPs) and play regulatory roles in a variety of biogenesis of mRNA. hnRNP A1 is a member of the hnRNP A/B subfamily, is highly abundant, and is involved in pre-mRNA and mRNA metabolism such as alternative splicing, mRNA export, splice site selection, mRNA turnover, and translation. Recent studies have shown that stress stimuli such as osmotic shock or UVC irradiation induce cytoplasmic accumulation of hnRNP A1. The cytoplasmic accumulation is concomitant with an increase in its phosphorylation and that requires p38 MAPK. We have previously demonstrated that hnRNP A1 protein shows diminished expression level and altered subcellular distribution in senescent HS74 fibroblasts. In this study, we observed that phosphorylated hnRNP A1 protein levels decreased as a result of MNK1 inhibition and that reciprocal binding occurs between hnRNP A1 and MNK1. These data implicate MNK1 as the kinase in the p38 MAPK pathway that activates hnRNP A1 in IMR-90 fibroblasts. Furthermore, we demonstrate that inhibition of MNK1 activity modulates the phosphorylation and subcellular distribution of hnRNP A1 protein. These results suggest a role for MNK1 in the regulation of hnRNP A1 in senescent cells. This is the first report, to our knowledge, that shows a link between MNK1 and cellular senescence.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Allemand E, Guil S, Myers M, Moscat J, Cáceres JF, Krainer AR (2005) Regulation of heterogeneous nuclear ribonucleoprotein A1 transport by phosphorylation in cells stressed by osmotic shock. Proc Natl Acad Sci U S A 102:3605–3610

    Article  PubMed  CAS  Google Scholar 

  • Bianchini A, Loiarro M, Bielli P, Busà R, Paronetto MP, Loreni F, Geremia R, Sette C (2008) Phosphorylation of eIF4E by MNKs supports protein synthesis, cell cycle progression and proliferation in prostate cancer cells. Carcinogenesis 29:2279–2288

    Article  PubMed  CAS  Google Scholar 

  • Bishop NA, Lu T, Yankner BA (2010) Neural mechanisms of ageing and cognitive decline. Nature 464:529–535

    Article  PubMed  CAS  Google Scholar 

  • Buxadé M, Parra JL, Rousseau S, Shpiro N, Marquez R, Morrice N, Bain J, Espel E, Proud CG (2005) The Mnks are novel components in the control of TNF alpha biosynthesis and phosphorylate and regulate hnRNP A1. Immunity 23:177–189

    Article  PubMed  Google Scholar 

  • Chen Z, Trotman LC, Shaffer D, Lin HK, Dotan ZA, Niki M, Koutcher JA, Scher HI, Ludwig T, Gerald W, Cordon-Cardo C, Pandolfi PP (2005) Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436:725–730

    Article  PubMed  CAS  Google Scholar 

  • Collado M, Blasco MA, Serrano M (2007) Cellular senescence in cancer and aging. Cell 130:223–233

    Article  PubMed  CAS  Google Scholar 

  • Coulthard LR, White DE, Jones DL, McDermott MF, Burchill SA (2009) p38(MAPK): stress responses from molecular mechanisms to therapeutics. Trends Mol Med 15:369–379

    Article  PubMed  CAS  Google Scholar 

  • Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, Peacocke M, Campisi J (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92:9363–9367

    Article  PubMed  CAS  Google Scholar 

  • Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA Jr, Butel JS, Bradley A (1992) Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356:215–221

    Article  PubMed  CAS  Google Scholar 

  • Dreyfuss G, Matunis MJ, Pinol-Roma S, Burd CG (1993) hnRNP proteins and the biogenesis of mRNA. Annu Rev Biochem 62:289–321

    Article  PubMed  CAS  Google Scholar 

  • Guil S, Long JC, Cáceres JF (2006) hnRNP A1 relocalization to the stress granules reflects a role in the stress response. Mol Cell Biol 26:5744–5758

    Article  PubMed  CAS  Google Scholar 

  • Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25:585–621

    Article  PubMed  CAS  Google Scholar 

  • He ZY, Wen H, Shi CB, Wang J (2010) Up-regulation of hnRNP A1, Ezrin, tubulin β-2C and Annexin A1 in sentinel lymph nodes of colorectal cancer. World J Gastroenterol 16:4670–4676

    Article  PubMed  CAS  Google Scholar 

  • Hubbard K, Dhanaraj SN, Sethi KA, Rhodes J, Wilusz J, Small MB, Ozer HL (1995) Alteration of DNA and RNA binding activity of human telomere binding proteins occurs during cellular senescence. Exp Cell Res 218:241–247

    Article  PubMed  CAS  Google Scholar 

  • Iwasa H, Han J, Ishikawa F (2003) Mitogen-activated protein kinase p38 defines the common senescence-signaling pathway. Genes Cells 8:131–144

    Article  PubMed  CAS  Google Scholar 

  • Jo OD, Martin J, Bernath A, Masri J, Lichtenstein A, Gera J (2008) Heterogeneous nuclear ribonucleoprotein A1 regulates cyclin D1 and c-myc internal ribosome entry site function through AKT signaling. J Biol Chem 283:23274–23287

    Article  PubMed  CAS  Google Scholar 

  • Kang S, Jung M, Kim CW, Shin DY (2005) Inactivation of p38 kinase delays the onset of senescence in rabbit articular chondrocytes. Mech Ageing Dev 126:591–597

    Article  PubMed  CAS  Google Scholar 

  • Knauf U, Tschopp C, Gram H (2001) Negative regulation of protein translation by mitogen-activated protein kinase-interacting kinases 1 and 2. Mol Cell Biol 21:5500–5511

    Article  PubMed  CAS  Google Scholar 

  • Maruyama J, Naguro I, Takeda K, Ichijo H (2009) Stress-activated MAP kinase cascades in cellular senescence. Curr Med Chem 16:1229–1235

    Article  PubMed  CAS  Google Scholar 

  • Molofsky AV, Slutsky SG, Joseph NM, He S, Pardal R, Krishnamurthy J, Sharpless NE, Morrison SJ (2006) Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443:448–452

    Article  PubMed  CAS  Google Scholar 

  • Nakielny S, Dreyfuss G (1997) Nuclear export of proteins and RNAs. Curr Opin Cell Biol 9:420–429

    Article  PubMed  CAS  Google Scholar 

  • Nicke B, Bastien J, Khanna SJ, Warne PH, Cowling V, Cook SJ, Peters G, Delpuech O, Schulze A, Berns K, Mullenders J, Beijersbergen RL, Bernards R, Ganesan TS, Downward J, Hancock DC (2005) Involvement of MINK, a Ste20 family kinase, in Ras oncogene-induced growth arrest in human ovarian surface epithelial cells. Mol Cell 20:673–685

    Article  PubMed  CAS  Google Scholar 

  • Pyronnet S (2000) Phosphorylation of the cap-binding protein eIF4E by the MAPK-activated protein kinase Mnk1. Biochem Pharmacol 60:1237–1243

    Article  PubMed  CAS  Google Scholar 

  • Reed JC (1999) Mechanisms of apoptosis avoidance in cancer. Curr Opin Oncol 11:68–75

    Article  PubMed  CAS  Google Scholar 

  • Salvatore MF, Pruett BS, Spann SL, Dempsey C (2009) Aging reveals a role for nigral tyrosine hydroxylase ser31 phosphorylation in locomotor activity generation. PLoS One 4:e8466

    Article  PubMed  Google Scholar 

  • Severino J, Allen RG, Balin S, Balin A, Cristofalo VJ (2000) Is beta-galactosidase staining a marker of senescence in vitro and in vivo? Exp Cell Res 257:162–171

    Article  PubMed  CAS  Google Scholar 

  • Shimada N, Rios I, Moran H, Sayers B, Hubbard K (2009) p38 MAP kinase-dependent regulation of the expression level and subcellular distribution of heterogeneous nuclear ribonucleoprotein A1 and its involvement in cellular senescence in normal human fibroblasts. RNA Biol 6:293–304

    Article  PubMed  CAS  Google Scholar 

  • Syntichaki P, Troulinaki K, Tavernarakis N (2007) eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans. Nature 445:922–926

    Article  PubMed  CAS  Google Scholar 

  • Takekawa M, Adachi M, Nakahata A, Nakayama I, Itoh F, Tsukuda H, Taya Y, Imai K (2000) p53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation. EMBO J 19:6517–6526

    Article  PubMed  CAS  Google Scholar 

  • Tavernarakis N (2007) Protein synthesis and aging: eIF4E and the soma vs. germline distinction. Cell Cycle 6:1168–1171

    Article  PubMed  CAS  Google Scholar 

  • van der Houven van Oordt W, Diaz-Meco MT, Lozano J, Krainer AR, Moscat J, Caceres JF (2000) The MKK(3/6)-p38-signaling cascade alters the subcellular distribution of hnRNP A1 and modulates alternative splicing regulation. J Cell Biol 149:307–316

    Article  PubMed  Google Scholar 

  • Waskiewicz AJ, Flynn A, Proud CG, Cooper JA (1997) Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2. EMBO J 16:1909–1920

    Article  PubMed  CAS  Google Scholar 

  • Widmann C, Gibson S, Jarpe MB, Johnson GL (1999) Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 79:143–180

    PubMed  CAS  Google Scholar 

  • Zhu D, Xu G, Ghandhi S, Hubbard K (2002) Modulation of the expression of p16INK4a and p14ARF by hnRNP A1 and A2 RNA binding proteins: implications for cellular senescence. J Cell Physiol 93:19–25

    Article  Google Scholar 

  • Ziaei S, Shimada N, Kucharavy H, Hubbard K (2012) MNK1 expression increases during cellular senescence and modulates the subcellular localization of hnRNP A1. Exp Cell Res 318:500–508

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, The City College of New York, 160 Convent Ave, New York, NY, 10031, USA

    Samira Ziaei & Naoko Shimada

Authors
  1. Samira Ziaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naoko Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Samira Ziaei .

Editor information

Editors and Affiliations

  1. Department of Biological Sciences, Kean University, Room 213, Library Building, Union, New Jersey, USA

    M.A. Hayat

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Ziaei, S., Shimada, N. (2014). Induction of Cellular Senescence: Role of Mitogen-Activated Protein Kinase-Interacting Kinase 1. In: Hayat, M. (eds) Tumor Dormancy, Quiescence, and Senescence, Volume 2. Tumor Dormancy and Cellular Quiescence and Senescence, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7726-2_12

Download citation

Publish with us

Policies and ethics

Search

Navigation