Noel A Warfel1, Wafik S El-Deiry. 1. Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Department of Medicine (Hematology/Oncology), Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA.
Abstract
PURPOSE OF REVIEW: This review provides an overview of the structure, regulation and physiological functions of p21, the product of the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene, with a focus on its dual role in promoting and repressing biological processes that are hallmarks of tumourigenesis. RECENT FINDINGS: Recent work has provided a better understanding of the molecular mechanisms of how oncogenic signalling pathways influence p21 expression. In response to cellular stimuli, p21 expression is tightly regulated at transcriptional and post-translational levels through mechanisms involving RNA stabilization, phosphorylation and ubiquitination. As a result, growing evidence reveals that several important tumour suppressor and oncogenic signalling pathways alter p21 expression to elicit their effects on cell cycle progression and survival. Thus, p21 expression can both promote and inhibit tumourigenic processes, depending on the cellular context. SUMMARY: Since its discovery, it has become increasingly clear that p21 can function as both a classical tumour suppressor and an oncogene. In order to effectively utilize p21 as a therapeutic target, it will be necessary to design therapeutic strategies that preferentially block the ability of p21 to promote senescence, stem cell renewal and cyclin/CDK activation, while leaving its tumour suppressive functions intact.
PURPOSE OF REVIEW: This review provides an overview of the structure, regulation and physiological functions of p21, the product of the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene, with a focus on its dual role in promoting and repressing biological processes that are hallmarks of tumourigenesis. RECENT FINDINGS: Recent work has provided a better understanding of the molecular mechanisms of how oncogenic signalling pathways influence p21 expression. In response to cellular stimuli, p21 expression is tightly regulated at transcriptional and post-translational levels through mechanisms involving RNA stabilization, phosphorylation and ubiquitination. As a result, growing evidence reveals that several important tumour suppressor and oncogenic signalling pathways alter p21 expression to elicit their effects on cell cycle progression and survival. Thus, p21 expression can both promote and inhibit tumourigenic processes, depending on the cellular context. SUMMARY: Since its discovery, it has become increasingly clear that p21 can function as both a classical tumour suppressor and an oncogene. In order to effectively utilize p21 as a therapeutic target, it will be necessary to design therapeutic strategies that preferentially block the ability of p21 to promote senescence, stem cell renewal and cyclin/CDK activation, while leaving its tumour suppressive functions intact.
Authors: Wei Zhang; Bin Yi; Chao Wang; Dongquan Chen; Sejong Bae; Shi Wei; Rong-Jun Guo; Changming Lu; Lisa L H Nguyen; Wei-Hsiung Yang; James W Lillard; Xingyi Zhang; Lizhong Wang; Runhua Liu Journal: Clin Cancer Res Date: 2015-12-28 Impact factor: 12.531
Authors: Yulong Chen; Masahiko Terajima; Yanan Yang; Li Sun; Young-Ho Ahn; Daniela Pankova; Daniel S Puperi; Takeshi Watanabe; Min P Kim; Shanda H Blackmon; Jaime Rodriguez; Hui Liu; Carmen Behrens; Ignacio I Wistuba; Rosalba Minelli; Kenneth L Scott; Johannah Sanchez-Adams; Farshid Guilak; Debananda Pati; Nishan Thilaganathan; Alan R Burns; Chad J Creighton; Elisabeth D Martinez; Tomasz Zal; K Jane Grande-Allen; Mitsuo Yamauchi; Jonathan M Kurie Journal: J Clin Invest Date: 2015-02-09 Impact factor: 14.808
Authors: Marietta Y W T Lee; Sufang Zhang; Szu Hua Sharon Lin; Xiaoxiao Wang; Zbigniew Darzynkiewicz; Zhongtao Zhang; Ernest Y C Lee Journal: Cell Cycle Date: 2013-12-03 Impact factor: 4.534