An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7

S. Shin, B. J. Sung, Y. S. Cho, H. J. Kim, N. C. Ha, Jong-Ik Hwang, C. W. Chung, Y. K. Jung, B. H. Oh

Research output: Contribution to journalArticle

620 Citations (Scopus)

Abstract

Survivin, an apoptosis inhibitor/cell-cycle regulator, is critically required for suppression of apoptosis and ensuring normal cell division in the G2/M phase of the cell cycle. It is highly expressed in a cell cycle-regulated manner and localizes together with caspase-3 on microtubules within centrosomes. Whether survivin is a physiologically relevant caspase inhibitor has been unclear due to the difficulties with obtaining correctly folded survivin and finding the right conditions for inhibition assay. In this study, recombinant, active human survivin was expressed in Escherichia coli and purified to homogeneity. The protein, existing as a homodimer in solution, binds caspase-3 and -7 tightly with dissociation constants of 20.9 and 11.5 nM, respectively, when evaluated by surface plasmon resonance spectroscopy. Consistently, survivin potently inhibits the cleavage of a physiological substrate poly(ADP-ribose) polymerase and an artificial tetrapeptide by caspase-3 and -7 in vitro with apparent inhibition constants of 36.0 and 16.5 nM, respectively. The data suggest that sequestering caspase-3 and -7 in inhibited states on microtubules is at least one mechanism of survivin in the suppression of default apoptosis in the G2/M phase. The localization of survivin on microtubules, which is essential for its function, should increase the protective activity at the action site.

Original languageEnglish
Pages (from-to)1117-1123
Number of pages7
JournalBiochemistry
Volume40
Issue number4
DOIs
Publication statusPublished - 2001 Jan 30
Externally publishedYes

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Caspase 7
Apoptosis Regulatory Proteins
Caspase 3
Cells
Microtubules
Cell Division
Cell Cycle
G2 Phase
Apoptosis
Centrosome
Caspase Inhibitors
Surface Plasmon Resonance
Poly(ADP-ribose) Polymerases
Surface plasmon resonance
Escherichia coli
Assays
Spectrum Analysis
Spectroscopy
Substrates
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Shin, S., Sung, B. J., Cho, Y. S., Kim, H. J., Ha, N. C., Hwang, J-I., ... Oh, B. H. (2001). An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry, 40(4), 1117-1123. https://doi.org/10.1021/bi001603q

An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. / Shin, S.; Sung, B. J.; Cho, Y. S.; Kim, H. J.; Ha, N. C.; Hwang, Jong-Ik; Chung, C. W.; Jung, Y. K.; Oh, B. H.

In: Biochemistry, Vol. 40, No. 4, 30.01.2001, p. 1117-1123.

Research output: Contribution to journalArticle

Shin, S, Sung, BJ, Cho, YS, Kim, HJ, Ha, NC, Hwang, J-I, Chung, CW, Jung, YK & Oh, BH 2001, 'An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7', Biochemistry, vol. 40, no. 4, pp. 1117-1123. https://doi.org/10.1021/bi001603q
Shin, S. ; Sung, B. J. ; Cho, Y. S. ; Kim, H. J. ; Ha, N. C. ; Hwang, Jong-Ik ; Chung, C. W. ; Jung, Y. K. ; Oh, B. H. / An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. In: Biochemistry. 2001 ; Vol. 40, No. 4. pp. 1117-1123.
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