TY - JOUR
T1 - Feedback, crosstalk and competition
T2 - Ingredients for emergent non‐linear behaviour in the pi3k/mtor signalling network
AU - Ghomlaghi, Milad
AU - Hart, Anthony
AU - Hoang, Nhan
AU - Shin, Sungyoung
AU - Nguyen, Lan K.
N1 - Funding Information:
Acknowledgments: We acknowledge the financial supports from the Victorian Cancer Agency, Australia’s National Breast Cancer Foundation and the Cancer Council Victoria, Australia.
Funding Information:
Funding: L.K.N. was supported by a Victorian Cancer Agency Mid‐Career Research Fellowship (MCRF18026), an Investigator Initiated Research Scheme grant from National Breast Cancer Foun‐ dation (IIRS‐20‐094); and the Metcalf Venture Grants Scheme administered by Cancer Council Vic‐ toria, Australia.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - The PI3K/mTOR signalling pathway plays a central role in the governing of cell growth, survival and metabolism. As such, it must integrate and decode information from both external and internal sources to guide efficient decision‐making by the cell. To facilitate this, the pathway has evolved an intricate web of complex regulatory mechanisms and elaborate crosstalk with neigh-bouring signalling pathways, making it a highly non‐linear system. Here, we describe the mechanistic biological details that underpin these regulatory mechanisms, covering a multitude of negative and positive feedback loops, feed‐forward loops, competing protein interactions, and crosstalk with major signalling pathways. Further, we highlight the non‐linear and dynamic network behav-iours that arise from these regulations, uncovered through computational and experimental studies. Given the pivotal role of the PI3K/mTOR network in cellular homeostasis and its frequent dysreg-ulation in pathologies including cancer and diabetes, a coherent and systems‐level understanding of the complex regulation and consequential dynamic signalling behaviours within this network is imperative for advancing biology and development of new therapeutic approaches.
AB - The PI3K/mTOR signalling pathway plays a central role in the governing of cell growth, survival and metabolism. As such, it must integrate and decode information from both external and internal sources to guide efficient decision‐making by the cell. To facilitate this, the pathway has evolved an intricate web of complex regulatory mechanisms and elaborate crosstalk with neigh-bouring signalling pathways, making it a highly non‐linear system. Here, we describe the mechanistic biological details that underpin these regulatory mechanisms, covering a multitude of negative and positive feedback loops, feed‐forward loops, competing protein interactions, and crosstalk with major signalling pathways. Further, we highlight the non‐linear and dynamic network behav-iours that arise from these regulations, uncovered through computational and experimental studies. Given the pivotal role of the PI3K/mTOR network in cellular homeostasis and its frequent dysreg-ulation in pathologies including cancer and diabetes, a coherent and systems‐level understanding of the complex regulation and consequential dynamic signalling behaviours within this network is imperative for advancing biology and development of new therapeutic approaches.
KW - Cancer
KW - Crosstalk
KW - Feedback loop
KW - Nonlinear dynamics
KW - PI3K/mTOR signalling
UR - http://www.scopus.com/inward/record.url?scp=85108715363&partnerID=8YFLogxK
U2 - 10.3390/ijms22136944
DO - 10.3390/ijms22136944
M3 - Review Article
C2 - 34203293
AN - SCOPUS:85108715363
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 13
M1 - 6944
ER -