期刊
CELL REPORTS
卷 35, 期 8, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2021.109162
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资金
- Fondation UQTR
- FRQ-NT [2018-NC-205752]
- FRQ-S [265445, 252405]
- NSERC [RGPIN-2019-06863, RGPAS-2019-00017, DGECR-2019-00326]
- CIHR [PJT-169138]
- CFI [36916]
- NSF [DGE-1256259]
- NIH [5T32GM007133, R01 GM134119]
- NIH Office of Research Infrastructure Programs [P40 OD010440]
The ERK/MAPK pathway plays a crucial role in cell proliferation regulation in Caenorhabditis elegans, with different isoforms of MPK-1 having specific effects on germline differentiation and stem cell proliferation. The study suggests a potential non-autonomous role of ERK/MAPK in stem cell proliferation across species and tissue types, with significant clinical implications for cancer and other diseases.
Extracellular-signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) is a major positive regulator of cell proliferation, which is often upregulated in cancer. However, few studies have addressed ERK/MAPK regulation of proliferation within a complete organism. The Caenorhabditis elegans ERK/MAPK ortholog MPK-1 is best known for its control of somatic organogenesis and germline differentiation, but it also stimulates germline stem cell proliferation. Here, we show that the germline-specific MPK-1B isoform promotes germline differentiation but has no apparent role in germline stem cell proliferation. By contrast, the soma-specific MPK-1A isoform promotes germline stem cell proliferation non-autonomously. Indeed, MPK-1A functions in the intestine or somatic gonad to promote germline proliferation independent of its other known roles. We propose that a non-autonomous role of ERK/MAPK in stem cell proliferation may be conserved across species and various tissue types, with major clinical implications for cancer and other diseases.
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