Insights from model organisms on the functions of the tumor suppressor protein LKB1: Zebrafish chips in

Yme U Van Der Velden,Anna-Pavlina G Haramis

doi:10.18632/aging.100319

Yme U Van Der Velden, Anna-Pavlina G Haramis

Open Access

https://doi.org/10.18632/aging.100319

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Abstract

The tumor suppressor LKB1 has emerged as a critical regulator of cell polarity and energy‐metabolism. Studies in diverse model organisms continue to unravel the pathways downstream of LKB1; the emerging picture is that the outcomes of LKB1 signaling are mediated by a plethora of tissue‐specific and context‐dependent effectors.

Highlights

In 1998, the gene responsible for the rare dominantly inherited disorder Peutz-Jeghers syndrome[1], characterized by gastrointestinal hamartomatous polyposis and an increased predisposition to cancer [2], was identified as LKB1, which encodes a serine/threonine protein kinase
Clues as to its function were first discovered only in 2003, when it was identified as the long sought-after kinase that activates the alpha subunit of AMP-activated protein kinase (AMPK) [5],[6], linking LKB1 signaling to energy– metabolism control
LKB1 has been found to phosphorylate 12 other AMPK-related kinases including the microtubule-affinity-regulating kinase (MARK1-4), brain specific kinase (BRSK1-2), nuclear AMPK-related kinase (NUAK1-2), salt-inducible kinase (SIK1-3) and SNF-related kinase (SNRK) [7,8]. These results suggest that LKB1 is an upstream “master regulator” of energy homeostasis, cell polarity, DNA damage and cell cycle control [9]

Summary

Introduction

In 1998, the gene responsible for the rare dominantly inherited disorder Peutz-Jeghers syndrome[1], characterized by gastrointestinal hamartomatous polyposis and an increased predisposition to cancer [2], was identified as LKB1, which encodes a serine/threonine protein kinase. We review the current understanding of LKB1 function in cellular polarity and energy metabolism derived from loss-offunction studies performed in different model organisms. Many aspects of the polarity defects in LKB1-deficient follicle cells were rescued by introduction of a phosphomimetic ampka mutant demonstrating the involvement of the LKB1-AMPK axis in polarization during early development [21].

Results

Conclusion