RRC ID |
55875
|
著者 |
Furuta T, Joo HJ, Trimmer KA, Chen SY, Arur S.
|
タイトル |
GSK-3 promotes S-phase entry and progression in C. elegans germline stem cells to maintain tissue output.
|
ジャーナル |
Development
|
Abstract |
Adult C. elegans germline stem cells (GSCs) and mouse embryonic stem cells (mESCs) exhibit a non-canonical cell cycle structure with an abbreviated G1 phase and phase-independent expression of Cdk2 and cyclin E. Mechanisms that promote the abbreviated cell cycle remain unknown, as do the consequences of not maintaining an abbreviated cell cycle in these tissues. In GSCs, we discovered that loss of gsk-3 results in reduced GSC proliferation without changes in differentiation or responsiveness to GLP-1/Notch signaling. We find that DPL-1 transcriptional activity inhibits CDK-2 mRNA accumulation in GSCs, which leads to slower S-phase entry and progression. Inhibition of dpl-1 or transgenic expression of CDK-2 via a heterologous germline promoter rescues the S-phase entry and progression defects of the gsk-3 mutants, demonstrating that transcriptional regulation rather than post-translational control of CDK-2 establishes the abbreviated cell cycle structure in GSCs. This highlights an inhibitory cascade wherein GSK-3 inhibits DPL-1 and DPL-1 inhibits cdk-2 transcription. Constitutive GSK-3 activity through this cascade maintains an abbreviated cell cycle structure to permit the efficient proliferation of GSCs necessary for continuous tissue output.
|
巻・号 |
145(10)
|
公開日 |
2018-5-14
|
DOI |
10.1242/dev.161042
|
PII |
dev.161042
|
PMID |
29695611
|
PMC |
PMC6001380
|
MeSH |
Animals
Caenorhabditis elegans / cytology
Caenorhabditis elegans / embryology*
Caenorhabditis elegans Proteins / genetics*
Caenorhabditis elegans Proteins / metabolism
Cell Differentiation / genetics
Cell Proliferation / genetics
Cyclin E / biosynthesis
Cyclin-Dependent Kinase 2 / biosynthesis*
Cyclin-Dependent Kinase 2 / genetics
Germ Cells / cytology*
Glycogen Synthase Kinase 3 / genetics
Glycogen Synthase Kinase 3 / metabolism*
RNA Interference
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Receptors, Notch / metabolism
S Phase / physiology*
Signal Transduction / genetics
Stem Cells / cytology*
Transcription Factors / genetics*
Transcription, Genetic / genetics
|
IF |
5.763
|
引用数 |
5
|
リソース情報 |
線虫 |
tm2223 |