PMID- 30629673
OWN - NLM
STAT- MEDLINE
DCOM- 20191022
LR  - 20200309
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 14
IP  - 1
DP  - 2019
TI  - The Tuberin and Cyclin B1 complex functions as a novel G2/M sensor of serum 
      conditions and Akt signaling.
PG  - e0210612
LID - 10.1371/journal.pone.0210612 [doi]
LID - e0210612
AB  - A great deal of ground breaking work has determined that the Tuberin and Hamartin 
      Complex function as a negative regulator of protein synthesis and cell cycle 
      progression through G1/S. This is largely attributed to the GTPase activity of 
      Tuberin that indirectly inhibits the mammalian target of rapamycin (mTOR). During 
      times of ample nutrition Tuberin is inhibited by growth factor signaling, 
      including direct phosphorylation by Akt/PKB, allowing for activation of mTOR and 
      subsequent protein synthesis. It is well rationalized that maintaining 
      homeostasis requires communication between cell growth (mTOR signaling) and cell 
      division (cell cycle regulation), however how this occurs mechanistically has not 
      been resolved. This work demonstrates that in the presence of high serum, and/or 
      Akt signaling, direct binding between Tuberin and the G2/M cyclin, Cyclin B1, is 
      stabilized and the rate of mitotic entry is decreased. Importantly, we show that 
      this results in an increase in cell size. We propose that this represents a novel 
      cell cycle checkpoint linking mitotic onset with the nutritional status of the 
      cell to control cell growth.
FAU - Fidalgo da Silva, Elizabeth
AU  - Fidalgo da Silva E
AD  - Department of Biological Sciences, University of Windsor, Windsor, Ontario, 
      Canada.
FAU - Botsford, Sabrina
AU  - Botsford S
AD  - Department of Biological Sciences, University of Windsor, Windsor, Ontario, 
      Canada.
FAU - Dare-Shih, Jessica
AU  - Dare-Shih J
AD  - Department of Biological Sciences, University of Windsor, Windsor, Ontario, 
      Canada.
FAU - Hanna, Miranda A
AU  - Hanna MA
AD  - Department of Biological Sciences, University of Windsor, Windsor, Ontario, 
      Canada.
FAU - Porter, Lisa A
AU  - Porter LA
AUID- ORCID: 0000-0002-9234-1712
AD  - Department of Biological Sciences, University of Windsor, Windsor, Ontario, 
      Canada.
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190110
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CCNB1 protein, human)
RN  - 0 (Cyclin B1)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Cyclin B1/*metabolism
MH  - *G2 Phase Cell Cycle Checkpoints
MH  - HEK293 Cells
MH  - Humans
MH  - *M Phase Cell Cycle Checkpoints
MH  - Mitosis
MH  - Protein Interaction Maps
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Serum/metabolism
MH  - *Signal Transduction
MH  - Tuberous Sclerosis Complex 2 Protein/*metabolism
PMC - PMC6328093
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/01/11 06:00
MHDA- 2019/10/23 06:00
PMCR- 2019/01/10
CRDT- 2019/01/11 06:00
PHST- 2018/05/08 00:00 [received]
PHST- 2018/12/30 00:00 [accepted]
PHST- 2019/01/11 06:00 [entrez]
PHST- 2019/01/11 06:00 [pubmed]
PHST- 2019/10/23 06:00 [medline]
PHST- 2019/01/10 00:00 [pmc-release]
AID - PONE-D-18-13847 [pii]
AID - 10.1371/journal.pone.0210612 [doi]
PST - epublish
SO  - PLoS One. 2019 Jan 10;14(1):e0210612. doi: 10.1371/journal.pone.0210612. 
      eCollection 2019.