Cyclin Oncogenic Activation

Murphy M, Stinnakre MG, Senamaud-Beaufort C et al 1997 Delayed early embryonic lethality following disruption of the murine cyclin A2 gene. Nat Genet 15 83—86 Nebreda AR, Hunt T 1993 The c-mos proto-oncogene protein kinase turns on and maintains the activity of MAP kinase, but not MPF, in cell-free extract of Xenopus oocytes and eggs. EMBO J 12 1979-1986... 

Oncogene-transformed mouse fibroblasts have a more decondensed chromatin structure than parental cell lines [59]. Phosphorylated Hl -3 levels are elevated in oncogene (ras, raf, fes, mos, myc) and aberrantly expressed MAPKK (MEK) transformed mouse fibroblasts, which have elevated activities of MAPK (ERKl and 2) [59] (Fig. 6). Further, RZ)-deficient human fibroblasts have increased levels of phosphorylated HI and a relaxed chromatin structure [60]. Cyclin E-Cdk2 was directly involved in increasing the levels of phosphorylated HI [60]. Elevated cyclin E-Cdk2 activity resulting from persistent activation of the Ras-MAPK pathway is also responsible for increased level of phosphorylated HI in oncogene-transformed mouse fibroblasts [61]. 

Figure 3. Oncogenic potential of ubiquitin ligases. MDM2 and Skp2 regulate levels of the tumor suppressors p53 and p27, respectively. Deregulated degradation of p53 and p27 results in cyclin E/cdk2 activation and cell proliferation.

Takada Y, Bhardwaj A, Potdar P, Aggarwal BB. 2004. Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin Dl, and abrogation of tumor cell proliferation. Oncogene 23 9247-9258. 

Berns K, Hijmans EM, Bernards R. Repression of c-Myc responsive genes in cycling cells causes G1 arrest through reduction of 54. cyclin E/CDK2 kinase activity. Oncogene 1997 15 1347-1356. 

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