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        Differential Ubiquitin Binding by the Acidic Loops of Ube2g1 and Ube2r1 Enzymes Distinguishes Their Lys-48-ubiquitylation Activities

        Choi, Yun-Seok,Lee, Yun-Ju,Lee, Seo-Yeon,Shi, Lei,Ha, Jung-Hye,Cheong, Hae-Kap,Cheong, Chaejoon,Cohen, Robert E.,Ryu, Kyoung-Seok American Society for Biochemistry and Molecular Bi 2015 The Journal of biological chemistry Vol.290 No.4

        <P>The ubiquitin E2 enzymes, Ube2g1 and Ube2r1, are able to synthesize Lys-48-linked polyubiquitins without an E3 ligase but how that is accomplished has been unclear. Although both E2s contain essential acidic loops, only Ube2r1 requires an additional C-terminal extension (184–196) for efficient Lys-48-ubiquitylation activity. The presence of Tyr-102 and Tyr-104 in the Ube2g1 acidic loop enhanced both ubiquitin binding and Lys-48-ubiquitylation and distinguished Ube2g1 from the otherwise similar truncated Ube2r1<SUP>1–183</SUP> (Ube2r1C). Replacement of Gln-105–Ser-106–Gly-107 in the acidic loop of Ube2r1C (Ube2r1C<SUP>YGY</SUP>) by the corresponding residues from Ube2g1 (Tyr-102–Gly-103–Tyr-104) increased Lys-48-ubiquitylation activity and ubiquitin binding. Two E2∼UB thioester mimics (oxyester and disulfide) were prepared to characterize the ubiquitin binding activity of the acidic loop. The oxyester but not the disulfide derivative was found to be a functional equivalent of the E2∼UB thioester. The ubiquitin moiety of the Ube2r1C<SUP>C93S</SUP>-[<SUP>15</SUP>N]UB<SUP>K48R</SUP> oxyester displayed two-state conformational exchange, whereas the Ube2r1C<SUP>C93S/YGY</SUP>-[<SUP>15</SUP>N]UB<SUP>K48R</SUP> oxyester showed predominantly one state. Together with NMR studies that compared UB<SUP>K48R</SUP> oxyesters of the wild-type and the acidic loop mutant (Y102G/Y104G) forms of Ube2g1, <I>in vitro</I> ubiquitylation assays with various mutation forms of the E2s revealed how the intramolecular interaction between the acidic loop and the attached donor ubiquitin regulates Lys-48-ubiquitylation activity.</P>

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        Epidural Lysis of Adhesions

        Lee, Frank,Jamison, David E.,Hurley, Robert W.,Cohen, Steven P. The Korean Pain Society 2014 The Korean Journal of Pain Vol.27 No.1

        As our population ages and the rate of spine surgery continues to rise, the use epidural lysis of adhesions (LOA) has emerged as a popular treatment to treat spinal stenosis and failed back surgery syndrome. There is moderate evidence that percutaneous LOA is more effective than conventional ESI for both failed back surgery syndrome, spinal stenosis, and lumbar radiculopathy. For cervical HNP, cervical stenosis and mechanical pain not associated with nerve root involvement, the evidence is anecdotal. The benefits of LOA stem from a combination of factors to include the high volumes administered and the use of hypertonic saline. Hyaluronidase has been shown in most, but not all studies to improve treatment outcomes. Although infrequent, complications are more likely to occur after epidural LOA than after conventional epidural steroid injections.

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        Review Article : Epidural Lysis of Adhesions

        ( Frank Lee ),( David E Jamison ),( Robert W Hurley ),( Steven P Cohen ) 대한통증학회 2014 The Korean Journal of Pain Vol.27 No.1

        As our population ages and the rate of spine surgery continues to rise, the use epidural lysis of adhesions (LOA) has emerged as a popular treatment to treat spinal stenosis and failed back surgery syndrome. There is moderate evidence that percutaneous LOA is more effective than conventional ESI for both failed back surgery syndrome, spinal stenosis, and lumbar radiculopathy. For cervical HNP, cervical stenosis and mechanical pain not associated with nerve root involvement, the evidence is anecdotal. The benefits of LOA stem from a combination of factors to include the high volumes administered and the use of hypertonic saline. Hyaluronidase has been shown in most, but not all studies to improve treatment outcomes. Although infrequent, complications are more likely to occur after epidural LOA than after conventional epidural steroid injections. (Korean J Pain 2014; 27: 3-15)

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