Failure of nuclear translocation and downregulation of NFATc1 is probably due to disruption of some of the following positive feedback mechanisms: 1) NFATc1-binding to the promoter/enhancer of the NFATc gene [30]; 2) activation of calcineurin transcription by NFATc [31]; and 3) induction of the IP3R1 gene as previously documented in neurons [32].
The failure of this translocation in response to insulin is one of the steps in the development of insulin resistance and type 2 diabetes.
In our opinion, the impairment of p38 MAPK activity likely contributes to the failure of HuR translocation in LPS-induced endotoxin tolerance or sepsis-induced immunoparalysis.
The loss of nuclear NF-κB is probably due to failure of NF-κB translocation in the nucleus and may be related to the inactivation of stress-activated protein kinases (SAPKs), such as MAPKs.
In addition, precautionary approaches are needed to minimize risks of translocation failures (maladaptation) that can be reduced through redundancy of multiple target sites.
The digestive tract insult often is underestimated, due to the lack of bedside tool to investigate its function; however, its alteration should not be considered, both as a victim of the circulatory failure and as a second source of organ failure through translocation and major source of endotoxemia.
In contrast to MCF-7 cells, MDA MB 231 cells, which exhibit distinct ER β expression but lack ER α expression (Li et al, 2010), restrict ERR β functionality leading to the failure of exogenous ER α translocation to the nucleus.
Transiently overexpressed WWOX is known to block nuclear translocation of many endogenous proteins21,22,23,25,29,30. Failure of p53/WWOX/Smad4 in undergoing nuclear translocation is probably due to the effect of WWOX.
The failure of chloramphenicol to completely abolish translocation may indicate that some of the bacteria possess the factors necessary to facilitate penetration while others may have to synthesize such components de novo[ 40].
Thus, after many translocations over more than a decade, it is premature to characterize any single translocation as a success or a failure, underscoring the need for a long view of translocation success.
