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Cellular senescence and aging: the role of B-MYB

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Title: Cellular senescence and aging: the role of B-MYB
Author(s): Mowla, SN
Lam, EW
Jat, PS
Item Type: Journal Article
Abstract: Cellular senescence is a stable cell cycle arrest, caused by insults, such as: telomere erosion, oncogene activation, irradiation, DNA damage, oxidative stress, and viral infection. Extrinsic stimuli such as cell culture stress can also trigger this growth arrest. Senescence is thought to have evolved as an example of antagonistic pleiotropy, as it acts as a tumor suppressor mechanism during the reproductive age, but can promote organismal aging by disrupting tissue renewal, repair, and regeneration later in life. The mechanisms underlying the senescence growth arrest are broadly considered to involve p16(INK4A) -pRB and p53-p21(CIP1/WAF1/SDI1) tumor suppressor pathways; but it is not known what makes the senescence arrest stable and what the critical downstream targets are, as they are likely to be key to the establishment and maintenance of the senescent state. MYB-related protein B (B-MYB/MYBL2), a member of the myeloblastosis family of transcription factors, has recently emerged as a potential candidate for regulating entry into senescence. Here, we review the evidence which indicates that loss of B-MYB expression has an important role in causing senescence growth arrest. We discuss how B-MYB acts, as the gatekeeper, to coordinate transit through the cell cycle, in conjunction with the multivulval class B (MuvB) complex and FOXM1 transcription factors. We also evaluate the evidence connecting B-MYB to the mTOR nutrient signaling pathway and suggest that inhibition of this pathway leading to an extension of healthspan may involve activation of B-MYB.
Publication Date: 1-Jul-2014
Date of Acceptance: 22-May-2014
URI: http://hdl.handle.net/10044/1/39228
DOI: http://dx.doi.org/10.1111/acel.12242
ISSN: 1474-9726
Publisher: Wiley
Start Page: 773
End Page: 779
Journal / Book Title: Aging Cell
Volume: 13
Issue: 5
Copyright Statement: © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: B-MYB
MuvB
aging
cellular senescence
growth arrest
Aging
Animals
Cell Aging
Cell Cycle Checkpoints
Cell Proliferation
Humans
Proto-Oncogene Proteins c-myb
Signal Transduction
Animals
Humans
Proto-Oncogene Proteins c-myb
Cell Aging
Signal Transduction
Cell Proliferation
Aging
Cell Cycle Checkpoints
Developmental Biology
11 Medical And Health Sciences
06 Biological Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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