The protein stability and transcriptional activity of p63α are regulated by SUMO-1 conjugation

Pamela Ghioni, Yuri D'Alessandra, Gelsomina Mansueto, Ellis Jaffray, Ronald T. Hay, Girolama La Mantia, Luisa Guerrini

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Post-translational modification of proteins by the ubiquitin-like molecule SUMO-1 regulates their stability and activity with crucial implications for many cellular processes. Here we show that p63α, but not p63β and γ, is sumoylated in vitro and in vivo at a single lysine residue, K637, in the post-SAM domain. SUMO-1 attachment targets ΔNp63α for proteasome mediated degradation while it does not influence p63α intracellular localization, as wild-type protein and a mutant earring the K637 mutated into arginine (K637R), have the same nuclear localization. Four natural p63 mutations, falling within the SAM and post-SAM domain of p63α, were found to be altered in their sumoylation capacity. The transcriptional activities of the natural mutants and of K637R were strongly increased compared to that of wild type p63, suggesting that sumoylation has a negative effect on p63 driven transcription. The findings that ΔNp63α protein levels are regulated by SUMO-1 and that this regulation is altered in natural p63 mutants, suggest that SUMO conjugation to p63 plays a critical role in regulating the biological activity of p63.

Original languageEnglish
Pages (from-to)183-190
Number of pages8
JournalCell Cycle
Volume4
Issue number1
Publication statusPublished - Jan 2005

Fingerprint

Sumoylation
Protein Stability
Ubiquitins
Proteasome Endopeptidase Complex
Transcription
Bioactivity
Lysine
Arginine
Proteins
Mutant Proteins
Post Translational Protein Processing
Ubiquitin
Degradation
Molecules
Mutation
Sterile Alpha Motif

Keywords

  • Development
  • p63
  • SUMO-1

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Ghioni, P., D'Alessandra, Y., Mansueto, G., Jaffray, E., Hay, R. T., La Mantia, G., & Guerrini, L. (2005). The protein stability and transcriptional activity of p63α are regulated by SUMO-1 conjugation. Cell Cycle, 4(1), 183-190.

The protein stability and transcriptional activity of p63α are regulated by SUMO-1 conjugation. / Ghioni, Pamela; D'Alessandra, Yuri; Mansueto, Gelsomina; Jaffray, Ellis; Hay, Ronald T.; La Mantia, Girolama; Guerrini, Luisa.

In: Cell Cycle, Vol. 4, No. 1, 01.2005, p. 183-190.

Research output: Contribution to journalArticle

Ghioni, P, D'Alessandra, Y, Mansueto, G, Jaffray, E, Hay, RT, La Mantia, G & Guerrini, L 2005, 'The protein stability and transcriptional activity of p63α are regulated by SUMO-1 conjugation', Cell Cycle, vol. 4, no. 1, pp. 183-190.
Ghioni P, D'Alessandra Y, Mansueto G, Jaffray E, Hay RT, La Mantia G et al. The protein stability and transcriptional activity of p63α are regulated by SUMO-1 conjugation. Cell Cycle. 2005 Jan;4(1):183-190.
Ghioni, Pamela ; D'Alessandra, Yuri ; Mansueto, Gelsomina ; Jaffray, Ellis ; Hay, Ronald T. ; La Mantia, Girolama ; Guerrini, Luisa. / The protein stability and transcriptional activity of p63α are regulated by SUMO-1 conjugation. In: Cell Cycle. 2005 ; Vol. 4, No. 1. pp. 183-190.
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