MASTL promotes cell contractility and motility through kinase-independent signaling.
Actin Cytoskeleton
/ enzymology
Cell Adhesion
/ genetics
Cell Cycle
/ genetics
Cell Line, Tumor
Cell Movement
/ genetics
Cell Nucleus
/ metabolism
Gene Expression Profiling
Humans
Integrins
/ genetics
Microtubule-Associated Proteins
/ deficiency
Nonmuscle Myosin Type IIB
/ genetics
Phosphorylation
Protein Binding
Protein Serine-Threonine Kinases
/ deficiency
Proteome
/ metabolism
RNA, Small Interfering
Rho Guanine Nucleotide Exchange Factors
/ genetics
Signal Transduction
/ genetics
Stress Fibers
/ genetics
Trans-Activators
/ genetics
Transcriptome
/ genetics
Tropomyosin
/ genetics
Vinculin
/ genetics
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
01 06 2020
01 06 2020
Historique:
received:
28
06
2019
revised:
03
02
2020
accepted:
11
03
2020
entrez:
21
4
2020
pubmed:
21
4
2020
medline:
20
3
2021
Statut:
ppublish
Résumé
Microtubule-associated serine/threonine-protein kinase-like (MASTL) is a mitosis-accelerating kinase with emerging roles in cancer progression. However, possible cell cycle-independent mechanisms behind its oncogenicity remain ambiguous. Here, we identify MASTL as an activator of cell contractility and MRTF-A/SRF (myocardin-related transcription factor A/serum response factor) signaling. Depletion of MASTL increased cell spreading while reducing contractile actin stress fibers in normal and breast cancer cells and strongly impairing breast cancer cell motility and invasion. Transcriptome and proteome profiling revealed MASTL-regulated genes implicated in cell movement and actomyosin contraction, including Rho guanine nucleotide exchange factor 2 (GEF-H1, ARHGEF2) and MRTF-A target genes tropomyosin 4.2 (TPM4), vinculin (VCL), and nonmuscle myosin IIB (NM-2B, MYH10). Mechanistically, MASTL associated with MRTF-A and increased its nuclear retention and transcriptional activity. Importantly, MASTL kinase activity was not required for regulation of cell spreading or MRTF-A/SRF transcriptional activity. Taken together, we present a previously unknown kinase-independent role for MASTL as a regulator of cell adhesion, contractility, and MRTF-A/SRF activity.
Identifiants
pubmed: 32311005
pii: 151688
doi: 10.1083/jcb.201906204
pmc: PMC7265322
pii:
doi:
Substances chimiques
ARHGEF2 protein, human
0
Integrins
0
MRTFA protein, human
0
Microtubule-Associated Proteins
0
Proteome
0
RNA, Small Interfering
0
Rho Guanine Nucleotide Exchange Factors
0
TPM4 protein, human
0
Trans-Activators
0
Tropomyosin
0
VCL protein, human
0
Vinculin
125361-02-6
MASTL protein, human
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Nonmuscle Myosin Type IIB
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancer Research UK
ID : A17196
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A12935
Pays : United Kingdom
Organisme : European Research Council
ID : 615258
Pays : International
Organisme : Cancer Research UK
ID : A12935
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P01058X/1
Pays : United Kingdom
Informations de copyright
© 2020 Taskinen et al.
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