News and Commentary
Published: 01 April 2005

IRES in distress: translational regulation of the inhibitor of apoptosis proteins XIAP and HIAP2 during cell stress

S M Lewis¹ &
M Holcik¹

Cell Death & Differentiation volume 12, pages 547–553 (2005)Cite this article

1303 Accesses
53 Citations
Metrics details

Members of the inhibitor of apoptosis (IAP) protein family are key regulators of programmed cell death. Recent investigations have determined that IAP function is tightly regulated by several mechanisms including translational regulation. The messenger RNA (mRNA) molecules for two IAP family members (XIAP and HIAP2) are translated using an internal ribosome entry site (IRES). The IRES mechanism allows for the continued translation of a protein under conditions where cap-dependent translation is inhibited such as apoptosis. Moreover, translational regulation of IAP expression via the IRES may allow for a rapid response to conditions in which the delay of cell death is desirable. In this review, we discuss the IRES-mediated translational regulation of XIAP and HIAP2 during transient cell stress, and highlight potential mechanisms and signaling pathways that may control the translational regulation of these two important inhibitors of apoptosis.

Cell damage occurs when a population encounters some type of stress (e.g. anoxia, UV or drug exposure, high temperature). If the stress is transient, cells may be able to repair the resulting damage; however, if the stress persists or the damage cannot be repaired, programmed cell death (also known as apoptosis) provides a means to remove the damaged and/or diseased cells from the population (reviewed in Vaux and Korsmeyer¹). Apoptosis is a tightly regulated process that requires a fine balance between pro- and antiapoptotic proteins, and this regulation prevents activation of the death program under inappropriate circumstances.

References

Vaux DL and Korsmeyer SJ (1999) Cell 96: 245–254
Salvesen GS and Abrams JM (2004) Oncogene 23: 2774–2784
Harada H and Grant S (2003) Rev. Clin. Exp. Hematol. 7: 117–138
Miller LK (1999) Trends Cell Biol. 9: 323–328
Holcik M et al. (1999) Nat. Cell Biol. 1: 190–192
Warnakulasuriyarachchi D et al. (2004) J. Biol. Chem. 279: 17148–17157
Van Eden ME et al. (2004) RNA 10: 469–481
Warnakulasuriyarachchi D, Ungureanu NH and Holcik M (2003) Cell. Death Differ. 10: 899–904
Liston P, Fong WG and Korneluk RG (2003) Oncogene 22: 8568–8580
Rothe M et al. (1995) Cell 83: 1243–1252
Roy N et al. (1995) Cell 80: 167–178
Liston P et al. (1996) Nature 379: 349–353
Ambrosini G, Adida C and Altieri DC (1997) Nat. Med. 3: 917–921
Hauser HP et al. (1998) J. Cell Biol. 141: 1415–1422
Kasof GM and Gomes BC (2001) J. Biol. Chem. 276: 3238–3246
Lagace M et al. (2001) Genomics 77: 181–188
Yang Y and Yu X (2003) FASEB J. 17: 790–799
Huang H et al. (2000) J. Biol. Chem. 275: 26661–26664
Suzuki Y, Nakabayashi Y and Takahashi R (2001) Proc. Natl. Acad. Sci. USA 98: 8662–8667
Tenev T et al. (2005) Nat. Cell Biol. 7: 70–77
Du C et al. (2000) Cell 102: 33–42
Verhagen AM et al. (2000) Cell 102: 43–53
Liston P et al. (2001) Nat. Cell Biol. 3: 128–133
Suzuki Y et al. (2001) Mol. Cell 8: 613–621
Creagh EM et al. (2004) J. Biol. Chem. 279: 26906–26914
MacFarlane M et al. (2002) J. Biol. Chem. 277: 36611–36616
Hu S and Yang X (2003) J. Biol. Chem. 278: 10055–10060
Wang CY et al. (1998) Science 281: 1680–1683
Hayden MS and Ghosh S (2004) Genes Dev. 18: 2195–2224
Kapp LD and Lorsch JR (2004) Annu. Rev. Biochem. 73: 657–704
Marissen WE and Lloyd RE (1998) Mol. Cell. Biol. 18: 7565–7574
Marissen WE et al. (2000) J. Biol. Chem. 275: 9314–9323
Saelens X, Kalai M and Vandenabeele P (2001) J. Biol. Chem. 276: 41620–41628
Jeffrey IW et al. (2002) Cancer Res. 62: 2272–2280
Holcik M, Sonenberg N and Korneluk RG (2000) Trends Genet. 16: 469–473
Hellen CU and Sarnow P (2001) Genes Dev. 15: 1593–1612
Van Eden ME et al. (2004) RNA 10: 720–730
Sherrill KW et al. (2004) J. Biol. Chem. 279: 29066–29074
Holcik M, Gordon BW and Korneluk RG (2003) Mol. Cell. Biol. 23: 280–288
Stoneley M et al. (2000) Nucleic Acids Res. 28: 687–694
Vagner S, Galy B and Pyronnet S (2001) EMBO Rep. 2: 893–898
Holcik M and Korneluk RG (2000) Mol. Cell. Biol. 20: 4648–4657
Meerovitch K (1993) J. Virol. 67: 3798–3807
Kim YK and Jang SK (1999) J. Gen. Virol. 80: 3159–3166
Ali N et al. (2000) J. Biol. Chem. 275: 27531–27540
Waysbort A et al. (2001) FEBS Lett. 490: 54–58
Ray PS and Das S (2002) Nucleic Acids Res. 30: 4500–4508
Kim YK et al. (2001) Nucleic Acids Res. 29: 5009–5016
Costa-Mattioli M, Svitkin Y and Sonenberg N (2004) Mol. Cell. Biol. 24: 6861–6870
Choi YD et al. (1986) Science 231: 1534–1539
Krecic AM and Swanson MS (1999) Curr. Opin. Cell Biol. 11: 363–371
Kim JH et al. (2003) Mol. Cell. Biol. 23: 708–720
Holcik M and Korneluk RG (2001) Nat. Rev. Mol. Cell. Biol. 2: 550–556
Holcik M et al. (2000) Oncogene 19: 4174–4177
Nevins TA et al. (2003) J. Biol. Chem. 278: 3572–3579
Pardo OE et al. (2003) Mol. Cell. Biol. 23: 7600–7610
Li W et al. (2004) Mol. Cell. Biol. 24: 10718–10732
Rutjes SA et al. (1999) Cell. Death Differ. 6: 976–986
Ayukawa K et al. (2000) J. Biol. Chem. 275: 34465–34470
Vassileva MT and Matunis MJ (2004) Mol. Cell. Biol. 24: 3623–3632
Intine RV et al. (2003) Mol. Cell 12: 1301–1307
Ohndorf UM et al. (2001) J. Biol. Chem. 276: 27188–27196
Santoro MF et al. (1998) J. Biol. Chem. 273: 13119–13128
Fladmark KE et al. (1999) Cell. Death Differ. 6: 1099–1108
Silverstein AM et al. (2002) Proc. Natl. Acad. Sci. USA 99: 4221–4226
Kong M et al. (2004) Science 306: 695–698
Simizu S, Tamura Y and Osada H (2004) Cancer Sci. 95: 266–270
Boe R et al. (1991) Exp. Cell Res. 195: 237–246
Kiguchi K et al. (1994) Cell Growth Differ. 5: 995–1004
Morimoto Y et al. (1997) Exp. Cell Res. 230: 181–186
Kwon TK (2001) Biochem. Biophys. Res. Commun. 287: 135–141
Nakielny S and Dreyfuss G (1996) J. Cell Biol. 134: 1365–1373
Lee HH et al. (2004) J. Cell Sci. 117: 5579–5589
Ishizaki T et al. (1996) EMBO J. 15: 1885–1893
Sebbagh M et al. (2001) Nat. Cell Biol. 3: 346–352
Amano M et al. (1996) J. Biol. Chem. 271: 20246–20249
Mills JC et al. (1998) J. Cell Biol. 140: 627–636
Esteve P et al. (1998) Oncogene 17: 1855–1869
Yamagiwa Y et al. (2004) Cancer Res. 64: 1293–1298
Zauberman A et al. (1999) Oncogene 18: 3886–3893
Morley SJ and McKendrick L (1997) J. Biol. Chem. 272: 17887–17893
Wang X et al. (1998) J. Biol. Chem. 273: 9373–9377
McKendrick L, Pain VM and Morley SJ (1999) Int. J. Biochem. Cell Biol. 31: 31–35
Marienfeld C et al. (2004) Gastroenterology 127: 1787–1797
Prevot D, Darlix JL and Ohlmann T (2003) Biol. Cell 95: 141–156
Henis-Korenblit S et al. (2000) Mol. Cell. Biol. 20: 496–506
Henis-Korenblit S et al. (2002) Proc. Natl. Acad. Sci. USA 99: 5400–5405
Cecconi F (1999) Cell Death Differ. 6: 1087–1098

Download references

Acknowledgements

We thank the members of our laboratory for critical reading of this manuscript and numerous discussions. The work in our laboratory is supported by funds from the Canadian Institutes of Health Research (CIHR), Canada Foundation for Innovation, and the Natural Science and Engineering Research Council of Canada (NSERC). MH is a CIHR New Investigator.

Author information

Authors and Affiliations

Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, 401 Smyth Road, Ottawa, Ontario, Canada, K1H 8L1
S M Lewis & M Holcik

Authors

S M Lewis
View author publications
Search author on:PubMed Google Scholar
M Holcik
View author publications
Search author on:PubMed Google Scholar

Corresponding author

Correspondence to M Holcik.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lewis, S., Holcik, M. IRES in distress: translational regulation of the inhibitor of apoptosis proteins XIAP and HIAP2 during cell stress. Cell Death Differ 12, 547–553 (2005). https://doi.org/10.1038/sj.cdd.4401602

Download citation

Published: 01 April 2005
Issue date: 01 June 2005
DOI: https://doi.org/10.1038/sj.cdd.4401602

This article is cited by

XIAP as a multifaceted molecule in Cellular Signaling
- Mina Hanifeh
- Farangis Ataei
Apoptosis (2022)
A repertoire of protease inhibitor families in Amblyomma americanum and other tick species: inter-species comparative analyses
- Lindsay M. Porter
- Željko M. Radulović
- Albert Mulenga
Parasites & Vectors (2017)
Reduced risk of apoptosis: mechanisms of stress responses
- Irina Milisav
- Borut Poljšak
- Samo Ribarič
Apoptosis (2017)
IRES inhibition induces terminal differentiation and synchronized death in triple-negative breast cancer and glioblastoma cells
- Christos Vaklavas
- William E. Grizzle
- Scott W. Blume
Tumor Biology (2016)
Inhibition of MDM2 homodimerization by XIAP IRES stabilizes MDM2, influencing cancer cell survival
- Tao Liu
- Hailong Zhang
- Muxiang Zhou
Molecular Cancer (2015)

IRES in distress: translational regulation of the inhibitor of apoptosis proteins XIAP and HIAP2 during cell stress

Log in or create a free account to read this content

References

Acknowledgements

Author information

Authors and Affiliations

Corresponding author

Rights and permissions

About this article

Cite this article

This article is cited by

XIAP as a multifaceted molecule in Cellular Signaling

A repertoire of protease inhibitor families in Amblyomma americanum and other tick species: inter-species comparative analyses

Reduced risk of apoptosis: mechanisms of stress responses

IRES inhibition induces terminal differentiation and synchronized death in triple-negative breast cancer and glioblastoma cells

Inhibition of MDM2 homodimerization by XIAP IRES stabilizes MDM2, influencing cancer cell survival

Search

Quick links

Log in or create a free account to read this content

References

Acknowledgements

Author information

Authors and Affiliations

Corresponding author

Rights and permissions

About this article

Cite this article

Share this article

This article is cited by

XIAP as a multifaceted molecule in Cellular Signaling

A repertoire of protease inhibitor families in Amblyomma americanum and other tick species: inter-species comparative analyses

Reduced risk of apoptosis: mechanisms of stress responses

IRES inhibition induces terminal differentiation and synchronized death in triple-negative breast cancer and glioblastoma cells

Inhibition of MDM2 homodimerization by XIAP IRES stabilizes MDM2, influencing cancer cell survival

Search

Quick links