PMID- 30301783
OWN - NLM
STAT- MEDLINE
DCOM- 20200107
LR  - 20211204
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Linking)
VI  - 131
IP  - 22
DP  - 2018 Nov 21
TI  - The RHEB-mTOR axis regulates expression of Tf2 transposons in fission yeast.
LID - jcs221457 [pii]
LID - 10.1242/jcs.221457 [doi]
AB  - The human TSC2 gene, mutations in which predispose individuals to the disease 
      tuberous sclerosis complex (TSC), encodes a GTPase-activating protein for the 
      GTPase RHEB. Loss of TSC2 results in constitutive activation of RHEB and its 
      target mammalian target of rapamycin (mTOR). We have previously reported that 
      fission yeast (Schizosaccharomyces pombe) Tf2 retrotransposons (hereafter Tf2s) 
      are abnormally induced upon nitrogen starvation in cells lacking the tsc2(+) gene 
      (Deltatsc2), a homolog of the human TSC2 gene, and in cells with a dominant-active 
      mutation in the fission yeast RHEB GTPase (rhb1-DA4). We report here that 
      induction of Tf2s in these mutants is suppressed upon overexpression of the 
      cgs2(+) gene, which encodes a cAMP-specific phosphodiesterase, or upon deletion 
      of components in the glucose/cAMP signaling pathway, namely Cyr1, Pka1, Tor1 and 
      the stress-activated transcription factor Atf1. The results suggest that the 
      glucose/cAMP signaling pathway is downregulated when cells are starved for 
      nitrogen. We also show that Tf2 proteins are degraded via autophagy, which is 
      under control of Tor2, a homolog of human mTOR. It appears that failure in the 
      two processes, downregulation of the glucose/cAMP signaling pathway and induction 
      of autophagy, allows abnormal induction of Tf2s upon nitrogen starvation in Deltatsc2 
      and rhb1-DA4 cells.
CI  - (c) 2018. Published by The Company of Biologists Ltd.
FAU - Nakase, Yukiko
AU  - Nakase Y
AUID- ORCID: 0000-0002-2669-5539
AD  - Radiation Biology Center, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto 
      606-8501, Japan.
FAU - Matsumoto, Tomohiro
AU  - Matsumoto T
AUID- ORCID: 0000-0001-6199-5126
AD  - Radiation Biology Center, Kyoto University, Yoshida-Konoe cho, Sakyo ku, Kyoto 
      606-8501, Japan tmatsumo@house.rbc.kyoto-u.ac.jp.
AD  - Graduate School of Biostudies, Kyoto University, Yoshida-Konoe cho, Sakyo ku, 
      Kyoto 606-8501, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181121
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Schizosaccharomyces pombe Proteins)
RN  - 0 (Tf2-6 protein, S pombe)
RN  - 0 (Tsc2 protein, S pombe)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
RN  - EC 3.6.5.2 (Rheb protein, S pombe)
RN  - N762921K75 (Nitrogen)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Monomeric GTP-Binding Proteins/genetics/*metabolism
MH  - Nitrogen/deficiency/metabolism
MH  - Schizosaccharomyces/genetics/metabolism
MH  - Schizosaccharomyces pombe Proteins/*biosynthesis/genetics/*metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
OTO - NOTNLM
OT  - Autophagy
OT  - Glucose/cAMP signaling
OT  - Nitrogen starvation
OT  - RHEB-mTOR
OT  - Transposon
OT  - Tuberous sclerosis complex
COIS- Competing interestsThe authors declare no competing or financial interests.
EDAT- 2018/10/12 06:00
MHDA- 2020/01/08 06:00
CRDT- 2018/10/11 06:00
PHST- 2018/06/11 00:00 [received]
PHST- 2018/10/01 00:00 [accepted]
PHST- 2018/10/12 06:00 [pubmed]
PHST- 2020/01/08 06:00 [medline]
PHST- 2018/10/11 06:00 [entrez]
AID - jcs.221457 [pii]
AID - 10.1242/jcs.221457 [doi]
PST - epublish
SO  - J Cell Sci. 2018 Nov 21;131(22):jcs221457. doi: 10.1242/jcs.221457.