Disease relevance of MTMR12

• These results indicate that the TP-3-PAP immunotoxin may be useful in the treatment of osteosarcoma and some soft tissue sarcomas [1].
• When TP-3-PAP (1.25 micrograms-10.0 micrograms) was given i.p. q.d. on days 3-5 after tumor inoculation, a dose-dependent reduction of the number of lung metastases was observed (P < 0.001) [1].

High impact information on MTMR12

• We have now identified myotubularin as the catalytically active 3-phosphatase subunit interacting with 3-PAP [2].
• Identification of myotubularin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adapter protein, 3-PAP [2].
• 3-PAP immunoprecipitates isolated from platelet cytosol hydrolyzed the D3-phosphate from PtdIns(3)P and PtdIns 3,4-bisphosphate [PtdIns(3,4)P(2)] [3].
• The 3-PAP sequence contains several motifs that predict interaction with proteins containing Src homology-2 (SH2) domains, phosphotyrosine-binding (PTB) domains, members of the 14-3-3 family, as well as proteins with SET domains [3].
• After 48 h no viable human OHS osteosarcoma cells were present in cultures containing TP-3-PAP as demonstrated by the absence of [3H]thymidine uptake into DNA [1].

Biological context of MTMR12

• However, coexpression of 3-PAP with myotubularin led to attenuation of the plasma membrane phenotype, associated with myotubularin relocalization to the cytosol [2].
• The IC50 of TP-3-PAP against OHS was 3.5 +/- 1.0 (SD) x 10(-12) M [1].

Anatomical context of MTMR12

• Association between 3-PAP and myotubularin was confirmed by reciprocal coimmunoprecipitation of both endogenous and recombinant proteins expressed in K562 cells [2].

Other interactions of MTMR12

• We have previously reported the identification of the 3-phosphatase adapter protein (3-PAP), a catalytically inactive member of the myotubularin gene family, which coprecipitates lipid phosphatidylinositol 3-phosphate-3-phosphatase activity from lysates of human platelets [2].
• Progression of the disease to the bone occurred in 20 patients: in 17 PSA was the first indicator of progression, in the other 3 PAP anticipated PSA for a very short time (3-4 months), which was not of relevance to clinical decisions [4].

References