SUMOylation does not affect cardiac troponin I stability but alters indirectly the development of force in response to Ca2+. (8th June 2022)

• Record Type: Journal Article
• Authors: Fertig, Bracy; Ling, Jiayue; Nollet, Edgar E.; Dobi, Sara; Busiau, Tara; Ishikawa, Kiyotake; Yamada, Kelly; Lee, Ahyoung; Kho, Changwon; Wills, Lauren; Tibbo, Amy J.; Scott, Mark; Grant, Kirsten; Campbell, Kenneth S.; Birks, Emma J.; MacQuaide, Niall; Hajjar, Roger; Smith, Godfrey L.; van der Velden, Jolanda; Baillie, George S.
• Is Part Of: FEBS journal. Volume 289:Number 20(2022)
• Page Start: 6267
• Page End: 6285
• Publication Date: 2022-06-08
• Subjects: heart failure -- myocytes -- myofilaments -- SUMO -- troponin I; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.16537
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Post‐translational modification of the myofilament protein troponin I by phosphorylation is known to trigger functional changes that support enhanced contraction and relaxation of the heart. We report for the first time that human troponin I can also be modified by SUMOylation at lysine 177. Functionally, TnI SUMOylation is not a factor in the development of passive and maximal force generation in response to calcium, however this modification seems to act indirectly by preventing SUMOylation of other myofilament proteins to alter calcium sensitivity and cooperativity of myofilaments. Utilising a novel, custom SUMO site‐specific antibody that recognises only the SUMOylated form of troponin I, we verify that this modification occurs in human heart and that it is upregulated during disease. Abstract : Post‐translational modification of the myofilament protein troponin I (TnI) by phosphorylation triggers changes that support enhanced heart contraction and relaxation. Here, George S. Baillie and colleagues report that TnI can also be modified by SUMOylation at lysine 177. This novel post‐translational modification is not a factor in the development of passive and maximal force generation in response to calcium; however, it acts indirectly to alter calcium sensitivity and cooperativity of myofilaments, by preventing SUMOylation of other myofilament proteins. Using a SUMO site‐specific antibody approach, they hereby show that this modification occurs in the human heart and is upregulated during disease.