Phosphorylation of MITF by AKT affects its downstream targets and causes TP53-dependent cell senescence.

Abstract

Microphthalmia-associated transcription factor (MITF) plays a crucial role in the melanogenesis and proliferation of melanocytes that is dependent on its abundance and modification. Here, we report that epidermal growth factor (EGF) induces senescence and cyclin-dependent kinase inhibitor 1A (CDKN1A) expression that is related to MITF. We found that MITF could bind TP53 to regulate CDKN1A. Furthermore, the interaction between MITF and TP53 is dependent on AKT activity. We found that AKT phosphorylates MITF at S510. Phosphorylated MITF S510 enhances its affinity to TP53 and promotes CDKN1A expression. Meanwhile, the unphosphorylative MITF promotes TYR expression. The levels of p-MITF-S510 are low in 90% human melanoma samples. Thus the level of p-MITF-S510 could be a possible diagnostic marker for melanoma. Our findings reveal a mechanism for regulating MITF functions in response to EGF stimulation and suggest a possible implementation for preventing the over proliferation of melanoma cells.

DOI: 10.1016/j.biocel.2016.09.029

Cite this paper

@article{Wang2016PhosphorylationOM, title={Phosphorylation of MITF by AKT affects its downstream targets and causes TP53-dependent cell senescence.}, author={Chenyao Wang and Lu Zhao and Qian Su and Xiaoyu Fan and Ying Wang and Shunqiang Gao and Huafei Wang and Huaiyong Chen and Chi Bun Chan and Zhixue Liu}, journal={The international journal of biochemistry & cell biology}, year={2016}, volume={80}, pages={132-142} }