The protein FAM72 (p17) signalling pathways in cancer

Fig-4_heese2

Schematic hypothesis of p17-mediated tumorigenesis by influencing p53 signalling pathways. During tomorigenesis p17 expression gets probably at two different loci (FAM72A/B) out of control. Upon DNA damage PPM1D regulates UNG2 action and suppresses BER through the modulation of various targets including p53 (via p38 MAP kinase). P17 interferes with BER activities either directly via UNG2 or indirectly via its influence on p53 cascades. Mutant alleles encoding hyperactive PPM1D isoforms result in enhanced suppression of p53 causing cancer. Family members of p53 can trans-activate the human YPEL3 gene. Through its association with TMEM115 at the mitochondria membrane p17 also controls pivotal signalling pathways related to apoptosis and cancer including Ca2+ signalling, NNAT and CDK5 activities. APE, apurinic/apyrimidinic endonuclease; ATR, ataxia telangiectasia and Rad3 related protein; PPM1D, protein phosphatase 1D magnesium-dependent delta isoform.

Reference:

The protein p17 signaling pathways in cancer.
Heese K.
Tumour Biol. 2013 Dec;34(6):4081-7. (pdf)

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