Identification of new human mastermind proteins defines a family that consists of positive regulators for notch signaling
Authors: Takahiro Nagase
Kenichi Harigaya
Motoo Kitagawa
Sey-En Lin
Toshinao Oyama
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Mastermind; Notch signaling; Drosophila; human Mastermind-2; human Mastermind-3
Affiliations: Department of Molecular and Tumor Pathology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

Abstract:  Mastermind (Mam) is one of the evolutionarily conserved elements of Notch signaling. Genetic analyses in Drosophila implicated it as an important positive regulator of the pathway. We show here identification of two new members of human Mam family (human Mastermind-2 (hMam-2) and human Mastermind-3 (hMam-3)), which retain characteristics similar to human Mastermind-1 (hMam-1) and Drosophila Mastermind. Both hMam-2 and hMam-3 stabilize and participate in the DNA-binding complex RBP-J/CBF-1 protein and the Notch intracellular domains that serve as intermediates of the signaling. Both hMam-2 and hMam-3 enhanced the activation of transcription from a target promoter by Notch signaling. However, we also show evidence that the activation of the target promoter by Notch3 and Notch4 is more efficiently potentiated by hMam-2 than by hMam-1 or -3. The multiplicity of Mam proteins in the mammalian system may help provide divergence to the strength of the Notch signals in different cell types. 

Retracted: No

PubPeer comments:
 The authors of this study put a lot of effort into the collection of complete data on pancreas transplantations. Such data is a valuable source of information. I have many concerns about the statistical analysis. In the Statistical analysis section authors mention only one test used (the Fisher s exact test). I have a concern that they used this test for all the calculations (no matter if any conditions were met, other tests considered; the Fisher s test was used for both quantitative and qualitative variables - which, obviously, is not correct!). Furthermore, the p-values are provided in table 1 as follows: ![file] it is not explained what is compared to what. Statistical tests results are expected to be reported in table 2 and 3 but those are lacking: ![file] Please notice that the use of means and medians should be justified by previous analysis of the distribution. Means should be reported along with standard deviations and medians with, e.g. interquartile ranges. Please calculate the mean difference, not the difference between means regarding P-PASS and PDRI, and provide confidence intervals. There is no censoring in the survival analysis - was the data complete? Authors wrote:  Table 1 lists the donor parameters taken into consideration in the aforementioned prediction models together with cold ischemia time, as included in one of these models. What prediction models are they talking about? There are none reported in any part of the manuscript. What do they mean by the sentence:  Each parameter was subject to normal distribution and was therefore useful for significance analysis ? It is a huge misunderstanding! Are the authors aware of nonparametric tests and analyzes? If all p-values are inevitably significant (I suppose the threshold was set at .05?) how can it be true:  The above analysis revealed no significant changes in pancreas transplant outcomes over a period of 18 years. ,