HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Summary Full Text Full Text (PDF) All Versions of this Article: fj.05-4184fjev1 20/8/1179    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Parcellier, A. Articles by Garrido, C. Search for Related Content PubMed PubMed Citation Articles by Parcellier, A. Articles by Garrido, C.

HSP27 favors ubiquitination and proteasomal degradation of p27^Kip1 and helps S-phase re-entry in stressed cells

Arnaud Parcellier^*,1, Mathilde Brunet^*,1, Elise Schmitt^*, Edwige Col, Céline Didelot^*, Arlette Hammann^*, Keiko Nakayama, Keiichi I. Nakayama, Saadi Khochbin, Eric Solary^* and Carmen Garrido^*,2

^* INSERM, Dijon, France;

INSERM U309, La Tronche, France;

Center for Translational and Advanced Animal Research on Human Diseases, Tohoku University, Miyagi, Japan; and

Division of Cell Biology, Medical Institute of Bioregulation, Kyushu University, Japan

²Correspondence: INSERM U517, IFR100, Faculty of Medicine, 7 boulevard Jeanne d’Arc, Dijon 21000, France. E-mail: cgarrido{at}u-bourgogne.fr

ABSTRACT

Stress-inducible HSP27 protects cells from death through various mechanisms. We have recently demonstrated that HSP27 can also enhance the degradation of some proteins through the proteasomal pathway. Here, we show that one of these proteins is the cyclin-dependent kinase (Cdk) inhibitor p27^Kip1. The ubiquitination and degradation of this protein that favors progression through the cell cycle was previously shown to involve either a Skp2-dependent mechanism, i.e., at the S-/G₂-transition, or a KPC (Kip1 ubiquitination-promoting complex)-dependent mechanism, i.e., at the G₀/G₁ transition. In this work, we demonstrate that, in response to serum depletion, p27^Kip1 cellular content first increases then progressively decreases as cells begin to die. In this stressful condition, HSP27 favors p27^Kip1 ubiquitination and degradation by the proteasome. A similar observation was made in response to stress induced by the NO donor glyceryl trinitrate (GTN). HSP27-mediated ubiquitination of p27^Kip1 does not require its phosphorylation on Thr¹⁸⁷ or Ser-10, nor does it depend on the SCF^Skp2 ubiquitin ligase E3 complex. It facilitates the G₁/S transition, which suggests that, in stressful conditions, HSP27 might render quiescent cells competent to re-enter the cell cycle.—Parcellier, A., Brunet, M., Schmitt, E., Col, E., Didelot, C., Hammann, A., Nakayama, K., Nakayama, K., Khochbin, S., Solary, E., Garrido, C. HSP27 favors ubiquitination and proteasomal degradation of p27^Kip1 and helps S-phase re-entry in stressed cells.

This article has been cited by other articles:

				N. Hedhli, L. Wang, Q. Wang, E. Rashed, Y. Tian, X. Sui, K. Madura, and C. Depre Proteasome activation during cardiac hypertrophy by the chaperone H11 Kinase/Hsp22 Cardiovasc Res, February 1, 2008; 77(3): 497 - 505. [Abstract] [Full Text] [PDF]