|ROWAN, SHELDON - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|CHANG, MIN-LEE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|REZNIKOV, NATALIE - Imperial College|
|TAYLOR, ALLEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
Submitted to: Experimental Eye Research
Publication Type: Review Article
Publication Acceptance Date: 2/29/2016
Publication Date: 3/3/2016
Citation: Rowan, S., Chang, M., Reznikov, N., Taylor, A. 2016. Disassembly of the lens fiber cell nucleus to create a clear lens: the p27 descent. Experimental Eye Research. 156:72-78. doi: 10.1016/j.exer.2016.02.011.
Technical Abstract: The eye lens is unique among tissues: it is transparent, does not form tumors, and the majority of its cells degrade their organelles, including their cell nuclei. A mystery for over a century, there has been considerable recent progress in elucidating mechanisms of lens fiber cell denucleation (LFCD). In contrast to the disassembly and reassembly of the cell nucleus during mitosis, LFCD is a unidirectional process that culminates in destruction of the fiber cell nucleus. Whereas p27Kip1, the cyclin-dependent kinase inhibitor, is upregulated during formation of LFC in the outermost cortex, in the inner cortex, in the nascent organelle free zone, p27Kip1 is degraded, markedly activating cyclin-dependent kinase 1 (Cdk1). This process results in phosphorylation of nuclear Lamins, dissociation of the nuclear membrane, and entry of lysosomes that liberate DNaseIIbeta (DLAD) to cleave chromatin. Multiple cellular pathways, including the ubiquitin proteasome system and the unfolded protein response, converge on post-translational regulation of p27Kip1. Mutations that impair these pathways are associated with congenital cataracts and loss of LFCD. These findings highlight new regulatory nodes in the lens and suggest that we are close to understanding this fascinating terminal differentiation process. Such knowledge may offer a new means to confront proliferative diseases including cancer.