USP2

A gene on chromosome 11q23.3 that encodes an enzyme which deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1. It plays a role in the G1/S cell cycle progression in normal and cancer cells, as well as in regulating myogenic differentiation of embryonic muscle cells. It is expressed in mesangial cells of the kidney and in different types of glomerulonephritides.

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USP2 was found to be stimulated by PTH in the bone.

Ezura, "PTHinduced osteoblast proliferation requires upregulation of the ubiquitin-specific peptidase 2 (Usp2) expression," Calcified Tissue International, vol.

Family Members USPL1, CYLD, USP1, USP2, USP3, USP4, USP5, USP6, USP7, USP YSP8, USP9x, USP10, USP11, USP12, USP13, USP14, USP15, USP16, USP17L2, USP18, USP19, USP20, USP21, USP22, USP23, USP24, USP25, USP26, USP27, USP28, USP29, USP30, USP31, USP32, USP33, USP34, USP35, USP36, USP37, USP38, USP39, USP40, USP41, USP42, USP43, USP44, USP45, USP46, USP47, USP48, USP49, USP50, USP51, USP52, USP53, USP54 OTUB1, OTUB2, OTUD1, OTUD3, OTUD4, OTUD5, OTUD6A, OTU OTUD6B, OTU1, HIN1L, A20, Cezanne, Cezanne2, TRABID, VCPIP1 UCH UCH-L1, UCH-L3, UCH37/UCH-L5, BAP1 Josephin ATXN3, ATXN3L, JOSD1, JOSD2 JAMM/MPN+ BRCC36, CSNS, POH1, AMSH, AMSH-LP, MPND, MYSM1, PRPF8 Table 2: Deubiquitinases and bone remodeling.

Deubiquitinating Enzymes and Bone Remodeling

USP2 participates in various cellular events, including circadian rhythm modulation [22], carcinogenesis [23], prevention of insulin resistance [24], and spermatogenesis [25].

For Western blot analysis, a 1000-fold dilution of antibodies against USP2 (AP2131a and AP2131c; Abgent, San Diego, CA), TRAF6 (ab33915; Abcam, Cambridge, UK), RelA (sc-372; Santa Cruz Biotechnology (SCB), Dallas, TX), p50 (sc-1190; SCB), I[kappa]B[alpha].

For detection of Western blot bands, corresponding to K48- and K63-linked ubiquitin chains, Oct proteins, HA-tagged ubiquitin, and V5-tagged USP2, 1000-fold-diluted antibodies against polyubiquitin chains formed by K48 residues (ab140601; Abcam) and K63 residues (ab179434; Abcam), Oct-1 (A301-717A; Bethyl Laboratories), Oct-2 (ab179808; Abcam), HA-tag (#3724; CST), and V5-tag (A190-120F; Bethyl Laboratories) were used as the primary antibodies.

LPS and Pam3CSK4 Repress the Expression of USP2 Splice Variants in Macrophages.

USP2 Knockdown (KD) Promotes LPS-Elicited Cytokine Production in Macrophage-Like HL-60 Cells.

We next investigated whether USP2 activates transcription of the cytokine genes by modifying chromatin accessibility after TLR stimulation.

We next investigated possible modulatory roles of the USP2 splice variants, USP2A and USP2B, in LPS-elicited cytokine production.

Ubiquitin-Specific Protease 2 Modulates the Lipopolysaccharide-Elicited Expression of Proinflammatory Cytokines in Macrophage-like HL-60 Cells

The DUBs, A20, CYLD, USP2, USP4, USP7, USP10, USP18, USP21, and USP25 terminate NF-[kappa]B signaling by removing K63-linked ubiquitin chains from signaling molecules [101-123].

Interplay between Inflammation and Sternness in Cancer Cells: The Role of Toll-Like Receptor Signaling

Downregulation of USP2, either induced by TNF treatment or artificially using siRNA, resulted in the prevention of TNF-induced apoptosis, an effect occurring in combination with increased levels of cellular FLICE-like inhibitory protein (cFLIP), an antiapoptotic molecule [46], and downregulation of Itch [10], which acts as a cFLIP inhibitor in that context [47].

TNF Tolerance in Monocytes and Macrophages: Characteristics and Molecular Mechanisms

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