title: HSP27 favors ubiquitination and proteasomal degradation of p27Kip1 and helps S-phase re-entry in stressed cells.
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 p27Kip1. 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, p27Kip1 cellular content first increases then progressively decreases as cells begin to die. In this stressful condition, HSP27favors p27Kip1 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 ofp27Kip1 does not require its phosphorylation on Thr187 or Ser-10, nor does it depend on the SCFSkp2 ubiquitin ligase E3 complex. It facilitates the G1/S transition,which suggests that, in stressful conditions, HSP27might render quiescent cells competent to re-enter the cell cycle.
authors.affiliation: INSERM, Dijon, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Parcellier
authors.forename: Mathilde
authors.initials: M
authors.lastname: Brunet
authors.forename: Elise
authors.initials: E
authors.lastname: Schmitt
authors.forename: Edwige
authors.initials: E
authors.lastname: Col
authors.forename: Céline
authors.initials: C
authors.lastname: Didelot
authors.forename: Arlette
authors.initials: A
authors.lastname: Hammann
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakayama
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
authors.forename: Saadi
authors.initials: S
authors.lastname: Khochbin
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.forename: Carmen
authors.initials: C
authors.lastname: Garrido
mesh_terms: D000818:Animals; D002460:Cell Line; D016895:Culture Media, Serum-Free; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000737:chemistry / Q000378:metabolism*; D016193:G1 Phase; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D016895:Culture Media, Serum-Free; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D044786:S-Phase Kinase-Associated Proteins; D025801:Ubiquitin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex