title: Targeting p27Kip1 protein: its relevance in the therapy of human cancer.
abstract: BACKGROUND
  Cell division cycle progression is achieved by a sequential and stringently concerted activation of a family of serine-threonine kinases, namely the cyclin-dependent kinases (CDKs). p27(Kip1) is a pivotal CDK inhibitor and a tight modulator of CDK-dependent phenotypes. Thus, p27(Kip1) plays a fundamental role in key cellular processes such as proliferation, differentiation, apoptosis, substrate adhesion and motility. Intriguingly, when p27(Kip1) is localized in the nucleus, it acts as an antiproliferative protein, while, in the cytosol, p27(Kip1) promotes cytoskeleton remodeling and might positively influence metastatization. Downregulation of p27(Kip1) nuclear level or its cytosolic mislocalization are consistently correlated with poor prognosis of numerous types of human epithelial and non-epithelial cancers.
  
  
  METHODS
  This review illustrates the basic structural features of p27(Kip1) protein, its metabolism and alterations in human malignancies, along with describing anticancer strategies based on targeting p27(Kip1).
  
  
  CONCLUSIONS
  Given the role of p27(Kip1) in the control of cell proliferation and its decreased level observed in malignancies with poor outcome, drugs able to handle the protein levels and localization might represent an important goal for novel specific and effective anticancer strategies. Although no convincing proofs have been reported, putative negative consequences of p27(Kip1) targeting might be also conceivable.
authors.affiliation: Second University of Naples, Medical School, Department of Biochemistry and Biophysics F. Cedrangolo, Via De Crecchio 7, 80138 Naples, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Borriello
authors.forename: Debora
authors.initials: D
authors.lastname: Bencivenga
authors.forename: Maria
authors.initials: M
authors.lastname: Criscuolo
authors.forename: Ilaria
authors.initials: I
authors.lastname: Caldarelli
authors.forename: Valeria
authors.initials: V
authors.lastname: Cucciolla
authors.forename: Annunziata
authors.initials: A
authors.lastname: Tramontano
authors.forename: Alessia
authors.initials: A
authors.lastname: Borgia
authors.forename: Annamaria
authors.initials: A
authors.lastname: Spina
authors.forename: Adriana
authors.initials: A
authors.lastname: Oliva
authors.forename: Silvio
authors.initials: S
authors.lastname: Naviglio
authors.forename: Fulvio
authors.initials: F
authors.lastname: Della Ragione
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; C436291:CDKN1B protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27