This study investigated the influence of expression of proteins of the INK4 family, particularly p16, on the growth and self-renewal kinetics of hematopoietic cells. First, retrovirus-mediated gene transfer (RMGT) was used to restore p16(INK4a) expression in the p16(INK4a)-deficient lymphoid and myeloid cell lines BV173 and K562, and it was confirmed that this inhibited their growth. Second, to...

The helix-loop-helix transcription factor Id1 coordinates cell growth and differentiation pathways within mammalian cells and has been implicated in regulating G(1)-S phase cell cycle transitions. Recently Id1 has been shown to repress Ets- and E-protein-mediated transactivation of p16/Ink4a. Because the p16/Ink4a protein has been demonstrated to be inactivated in subsets of familial and sporad...

Cyclin-dependent kinase inhibitor p16(INK4a) is implicated in replicative senescence, cell immortalization, and tumor generation. However, the mechanism regulating its overexpression in senescent cells is unknown. We used the enhanced green fluorescent protein reporter system to scan regulatory elements in the upstream region of p16(INK4a). The results of 5'-deletion studies indicated that the ...

BACKGROUND p16(INK4a) and p21(WAF1) are two independent cyclin-dependent kinase inhibitors encoded by the CDKN2A and CDKN1A genes, respectively. p16(INK4a) and p21(WAF1) are similarly involved in various anti-cancer processes, including the regulation of the critical G1 to S phase transition of the cell cycle, senescence and apoptosis. Therefore, we sought to elucidate the molecular mechanisms ...

Dysfunctional telomeres limit cellular proliferative capacity by activating the p53-p21- and p16(INK4a)-Rb-dependent DNA damage responses (DDRs). The p16(INK4a) tumor suppressor accumulates in aging tissues, is a biomarker for cellular senescence, and limits stem cell function in vivo. While the activation of a p53-dependent DDR by dysfunctional telomeres has been well documented in human cells...

OBJECTIVE Age-associated cellular senescence is thought to promote vascular dysfunction. p16(INK4a) is a cell cycle inhibitor that promotes senescence and is upregulated during normal aging. In this study, we examine the contribution of p16(INK4a) overexpression to venous thrombosis. METHODS AND RESULTS Mice overexpressing p16(INK4a) were studied with 4 different vascular injury models: (1) f...

OBJECTIVE A genomic region near the CDKN2A locus, encoding p16(INK4a), has been associated to type 2 diabetes and atherosclerotic vascular disease, conditions in which inflammation plays an important role. Recently, we found that deficiency of p16(INK4a) results in decreased inflammatory signaling in murine macrophages and that p16(INK4a) influences the phenotype of human adipose tissue macroph...

Telomere attrition in primary human fibroblasts induces replicative senescence accompanied by activation of the p53 and p16(INK4a)/RB tumor suppressor pathways. Although the contribution of p53 and its target, p21, to telomere-driven senescence have been well established, the role of p16(INK4a) is controversial. Attempts to dissect the significance of p16(INK4a) in response to telomere shorteni...

Recently, we read the article "P16(INK4a) overexpression and survival in osteosarcoma patients: a meta analysis" by Jie Bu and his colleagues, published in the recent issue of International Journal Of Experimental Pathology. This research performed a meta-analysis to uncover the role of P16(INK4a) expression in overall survival rate in patients with osteosarcoma. The investigators concluded as ...

OBJECTIVE In cervical intraepithelial neoplasia (CIN), p16(INK4a) immunohistochemistry has been reported to be a useful diagnostic biomarker. However, limited information is available about the association between the p16(INK4a) immunohistochemistry and the outcomes of CIN. Here, we report p16(INK4a) immunohistochemistry as an effective biomarker to predict the outcomes of CIN. METHODS p16(IN...