Identification of novel MARK3 substrates and upstream regulators

Abstract

MARK3, also known as Cdc25c-associated protein kinase (c-tak-1), is a
serine/threonine specific kinase that has been implicated in the regulation of crucial cellular programs such as cell signalling, cell adhesion, transcription regulation and cell cycle control. Since deregulation of these programs is linked to cancer development and progression, MARK3 is asstuned to participate in tumour formation.
This hypothesis is supported by the fact that upstream regulators of MARK3 comprise tumour suppressor and oncogenic kinases.
This project aimed to characterize the position of MARK3 within the cellular network more precisely by identifying novel substrates and upstream kinases of MARK3.
These results should lead to novel insights into the MARK3 ftmction(s) of MARK3
and concu1Tently shed light 011 the potential role of MARK3 in cancer development.
Kinesin family member C3 (KIFC3) is a microtubule minus end-directed motor
protein, and Kinesin light chain (KLC4) was identified as novel MARK3 substrate.
Kinesins are motor proteins that transport membraneous organelles and
macromolecules along microtubules. These findings indicate a novel role for MARK3
in cellular transpo1t or cellular transpo1t -dependent functions. Further efforts
identified a novel MARK3 phosphorylating kinase of 60 kDa, which is of substantial
interest since MARK3 upstream regulators may be used as therapeutical targets.

Date of Award	Apr 2009
Original language	English
Awarding Institution	Bangor University
Supervisor	Jurgen Muller (Supervisor)