title: Cyclin-dependent kinase 2 (CDK2) is a key mediator for EGF-induced cell transformation mediated through the ELK4/c-Fos signaling pathway.
abstract: Cyclin-dependent kinase 2 (CDK2) is a known regulator in the cell cycle control of the G1/S and S/G2 transitions. However, the role of CDK2 in tumorigenesis is controversial. Evidence from knockout mice as well as colon cancer cell lines indicated that CDK2 is dispensable for cell proliferation. In this study, we found that ectopic CDK2 enhances Ras (G12V)-induced foci formation and knocking down CDK2 expression markedly decreases epidermal growth factor (EGF)-induced cell transformation mediated through the downregulation of c-fos expression. Interestingly, CDK2 directly phosphorylates ELK4 at Thr194 and Ser387 and regulates the ELK4 transcriptional activity, which serves as a mechanism to regulate c-fos expression. In addition, ELK4 is overexpressed in melanoma and knocking down the ELK4 or CDK2 expression significantly attenuated the malignant phenotype of melanoma cells. Taken together, our study reveals a novel function of CDK2 in EGF-induced cell transformation and the associated signal transduction pathways. This indicates that CDK2 is a useful molecular target for the chemoprevention and therapy against skin cancer.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.|The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: C
authors.initials: C
authors.lastname: Peng
authors.affiliation: The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: W
authors.initials: W
authors.lastname: Zeng
authors.affiliation: The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: J
authors.initials: J
authors.lastname: Su
authors.affiliation: The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Y
authors.initials: Y
authors.lastname: He
authors.affiliation: The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: S
authors.initials: S
authors.lastname: Zhao
authors.affiliation: The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: W
authors.initials: W
authors.lastname: Ma
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Bode
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.affiliation: The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2 / Q000096:biosynthesis / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D015533:Transcriptional Activation / Q000235:genetics; D050808:ets-Domain Protein Elk-4 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C494193:ELK4 protein, human; D016760:Proto-Oncogene Proteins c-fos; D050808:ets-Domain Protein Elk-4; D004815:Epidermal Growth Factor; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2