An actin-WHAMM interaction linking SETD2 and autophagy.
Actins
/ metabolism
Autophagy
/ genetics
Autophagy-Related Proteins
/ genetics
Carcinoma, Renal Cell
/ genetics
Cell Line
Cell Line, Tumor
Down-Regulation
Gene Knockout Techniques
Histone-Lysine N-Methyltransferase
/ deficiency
Humans
Kidney Neoplasms
/ genetics
Membrane Proteins
/ metabolism
Microtubule-Associated Proteins
/ metabolism
Actin
Autophagy
Renal cell carcinoma
SETD2
WHAMM
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
18 06 2021
18 06 2021
Historique:
received:
01
09
2020
accepted:
09
09
2020
pubmed:
11
10
2020
medline:
24
8
2021
entrez:
10
10
2020
Statut:
ppublish
Résumé
The process of autophagy is dysregulated in many cancers including clear cell renal cell carcinoma (ccRCC). Autophagy involves the coordination of numerous autophagy-related (ATG) genes, as well as processes involving the actin cytoskeleton. The histone methyltransferase SETD2, frequently inactivated in ccRCC, has recently been shown to also methylate cytoskeletal proteins, which in the case of actin lysine 68 trimethylation (ActK68me3) regulates actin polymerization dynamics. Here we show that cells lacking SETD2 exhibit autophagy defects, as well as decreased interaction of the actin nucleation promoting factor WHAMM with its target actin, which is required for initiation of autophagy. Interestingly, the WHAMM actin binding deficit could be rescued with pharmacologic induction of actin polymerization in SETD2-null cells using Jasplakinolide. These data indicate that the decreased interaction between WHAMM and its target actin in SETD2-null cells was secondary to altered actin dynamics rather than loss of the SETD2 ActK68me3 mark itself, and underscores the importance of the functional defect in actin polymerization in SETD2-null cells exhibiting autophagy defects.
Identifiants
pubmed: 33036756
pii: S0006-291X(20)31766-6
doi: 10.1016/j.bbrc.2020.09.025
pmc: PMC8021614
mid: NIHMS1636715
pii:
doi:
Substances chimiques
Actins
0
Autophagy-Related Proteins
0
Membrane Proteins
0
Microtubule-Associated Proteins
0
WHAMM protein, human
0
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
SETD2 protein, human
EC 2.1.1.43
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
202-208Subventions
Organisme : NCI NIH HHS
ID : P30 CA125123
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES030285
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA203012
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA231993
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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