Deubiquitinase MYSM1

Definition:

Metalloprotease with deubiquitinase activity that plays important regulator roles in hematopoietic stem cell function, blood cell production and immune response. Participates in the normal programming of B-cell responses to antigen after the maturation process (By similarity). Within the cytoplasm, plays critical roles in the repression of innate immunity and autoimmunity. Removes 'Lys-63'-linked polyubiquitins from TRAF3 and TRAF6 complexes (By similarity). Attenuates NOD2-mediated inflammation and tissue injury by promoting 'Lys-63'-linked deubiquitination of RIPK2 component (By similarity). Suppresses the CGAS-STING1 signaling pathway by cleaving STING1 'Lys-63'-linked ubiquitin chains. In the nucleus, acts as a hematopoietic transcription regulator derepressing a range of genes essential for normal stem cell differentiation including EBF1 and PAX5 in B-cells, ID2 in NK-cell progenitor or FLT3 in dendritic cell precursors. Deubiquitinates monoubiquitinated histone H2A, a specific tag for epigenetic transcriptional repression, leading to dissociation of histone H1 from the nucleosome.

References:

[1]. Xiao-Xia Jiang, et al. Control of B cell development by the histone H2A deubiquitinase MYSM1. Immunity. 2011 Dec 23;35(6):883-96. [Content Brief]

[2]. Mingfu Tian, et al. MYSM1 Represses Innate Immunity and Autoimmunity through Suppressing the cGAS-STING Pathway. Cell Rep. 2020 Oct 20;33(3):108297. [Content Brief]

[3]. Ping Zhu, et al. A histone H2A deubiquitinase complex coordinating histone acetylation and H1 dissociation in transcriptional regulation. Mol Cell. 2007 Aug 17;27(4):609-21. [Content Brief]

[4]. Vijayalakshmi Nandakumar, et al. Epigenetic control of natural killer cell maturation by histone H2A deubiquitinase, MYSM1. Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):E3927-36. [Content Brief]

[5]. Ehsan Bahrami, et al. Myb-like, SWIRM, and MPN domains 1 (MYSM1) deficiency: Genotoxic stress-associated bone marrow failure and developmental aberrations. J Allergy Clin Immunol. 2017 Oct;140(4):1112-1119. [Content Brief]

[6]. Tangui Le Guen, et al. An in vivo genetic reversion highlights the crucial role of Myb-Like, SWIRM, and MPN domains 1 (MYSM1) in human hematopoiesis and lymphocyte differentiation. J Allergy Clin Immunol. 2015 Dec;136(6):1619-1626.e5. [Content Brief]

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