p57(Kip2) and cancer: time for a critical appraisal.

p57(Kip2) is a cyclin-dependent kinase inhibitor belonging to the Cip/Kip family, which also includes p21(Cip1) and p27(Kip1). So far, p57(Kip2) is the least-studied Cip/Kip protein, and for a long time its relevance has been related mainly to its unique role in embryogenesis. Moreover, genetic and molecular studies on animal models and patients with Beckwith-Wiedemann syndrome have shown that alterations in CDKN1C (the p57(Kip2) encoding gene) have functional relevance in the pathogenesis of this disease.

Targeting p27Kip1 protein: its relevance in the therapy of human cancer.

Introduction: 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.

p57Kip2 is a downstream effector of BCR-ABL kinase inhibitors in chronic myelogenous leukemia cells.

Chronic myelogenous leukemia (CML) is characterized by the expression of BCR-ABL tyrosine kinase, which results in increased cell proliferation and inhibition of apoptosis. In this study, we show that BCR-ABL-positive CML cell lines treated with imatinib (STI571) undergo G₁ cell cycle arrest associated with the accumulation of p57(Kip)², a cyclin-dependent kinase inhibitor (CKI). Interestingly, p57(Kip)² increase precedes the reported STI571-dependent upregulation of p27(Kip)¹.

Dietary polyphenols: focus on resveratrol, a promising agent in the prevention of cardiovascular diseases and control of glucose homeostasis.

Plants continuously produce an extraordinary variety of biologically active low-molecular-mass compounds. Among them, resveratrol (3,5,4'-trihydroxystilbene) is endowed with significant positive activities by protecting against cardiovascular diseases and preventing the development and progression of atherosclerosis. Furthermore, the molecule significantly ameliorates glucose homeostasis in obese mice.

EPO receptor gain-of-function causes hereditary polycythemia, alters CD34 cell differentiation and increases circulating endothelial precursors.

Background: Gain-of-function of erythropoietin receptor (EPOR) mutations represent the major cause of primary hereditary polycythemia. EPOR is also found in non-erythroid tissues, although its physiological role is still undefined.

Methodology/principal Findings: We describe a family with polycythemia due to a heterozygous mutation of the EPOR gene that causes a G-->T change at nucleotide 1251 of exon 8.