MAPO1

Last week I wrote about the possible contribution to renal tumourigenesis posed by inactivation (or deregulation) of DNA repair enzymes. Following on from that theme I found a paper by Komori et al, 2009* in Oncogene entitled ‘A novel protein, MAPO1, that functions in apoptosis triggered by O6-methylguanine mispair in DNA’. In it, the authors theorise that the protein MAPO1 may participate in the signalling cascade downstream of the DNA repair protein MGMT.

MGMT is responsible for the detection and repair of DNA damage caused by alkylating agents. If the damage is severe enough then the repair mechanism is bypassed, and to prevent transition mutations being propagated after DNA replication, apoptosis is initiated by MGMT via MAPO1, as the authors suggest.

So how is this relevant to BHD Syndrome? MAPO1 also goes by the name FNIP2. The relationship between FNIP2 and FLCN is not fully understood but could FLCN have any role in regulating FNIP2 activity in apoptosis induction in response to alkylating damage? Could this facet contribute to the accumulation of genetic instability in tissues with high cell turnover and metabolism (i.e. the kidneys) and could we speculate that this could contribute to the development of malignant tumours in the kidneys of BHD patients as opposed to any other organ since the kidneys are exposed to high levels of external chemicals due to their role in filtering urine?

Komori, K., Takagi, Y., Sanada, M., Lim, T.-H., Nakatsu, Y., Tsuzuki, T., Sekiguchi, M., Hidaka, M. A novel protein, MAPO1, that functions in apoptosis triggered by O(6)-methylguanine mispair in DNA. Oncogene 28: 1142-1150, 2009.

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