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dale Haines, PhD

Associate Professor, Biochemistry

Associate Professor, Fels Institute for Cancer Research and Molecular Biology

Telephone:  215-707-5765

Fax:  215-707-2805

Email: dhaines@temple.edu

Department of Biochemistry

Fels Institute for Cancer Research and Molecular Biology

Hahnemann University (1992)

 

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Ubiquitination is an essential, highly conserved and common protein modification event that results in the covalent attachment of a 76 amino acid polypeptide called ubiquitin to a lysine residue of a targeted substrate. Ubiquitin modification is a multi-step process and requires the coordinated activity of at least three enzymes. These are a ubiquitin activating enzyme (E1), an ubiquitin conjugating enzyme (E2) and a specificity factor or complex (E3) that functions in substrate recognition. Ubiquitination modulates protein function in multiple ways. The most common is poly-ubiquitinated (through lysine 48 linkages) mediated targeting of substrates to the proteasome. Modification of substrates in other ways (e.g. mono-ubiquitination or poly-ubiquitination through Lys 63 linkages) by the E1-E2-E3 cascade regulates protein function by mechanisms that are independent of promoting their degradation or facilitates their destruction by proteasome-independent mechanisms. My laboratory is interested in studying E3 ligase-substrate interactions (both in yeast and in mammalian cells) and how such associations impinge on substrate expression and function as well as on normal cellular physiology. We are also interested in understanding how highly conserved Cdc48 containing complexes function in targeting ubiquitinated substrates to the proteasome in yeast and mammalian cells and how suppression of Cdc48 and adapter function affects specific biological processes, including tumor cell proliferation.

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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

19061897. Bhattacharya S, Shcherbik N, Vasilescu J, Smith JC, Figeys D, Haines DS, Identification of lysines within membrane-anchored Mga2p120 that are targets of Rsp5p ubiquitination and mediate mobilization of tethered Mga2p90. J Mol Biol 385:3(718-25)2009 Jan 23

18212250. Li JG, Haines DS, Liu-Chen LY, Agonist-promoted Lys63-linked polyubiquitination of the human kappa-opioid receptor is involved in receptor down-regulation. Mol Pharmacol 73:4(1319-30)2008 Apr

17719829. Bhattacharya S, Zoladek T, Haines DS, WW domains 2 and 3 of Rsp5p play overlapping roles in binding to the LPKY motif of Spt23p and Mga2p. Int J Biochem Cell Biol 40:1(147-57)2008

17483323. Carbone CJ, Graña X, Reddy EP, Haines DS, p21 loss cooperates with INK4 inactivation facilitating immortalization and Bcl-2-mediated anchorage-independent growth of oncogene-transduced primary mouse fibroblasts. Cancer Res 67:9(4130-7)2007 May 1

17289586. Shcherbik N, Haines DS, Cdc48p(Npl4p/Ufd1p) binds and segregates membrane-anchored/tethered complexes via a polyubiquitin signal present on the anchors. Mol Cell 25:3(385-97)2007 Feb 9

16230384. Nagl NG Jr, Patsialou A, Haines DS, Dallas PB, Beck GR Jr, Moran E, The p270 (ARID1A/SMARCF1) subunit of mammalian SWI/SNF-related complexes is essential for normal cell cycle arrest. Cancer Res 65:20(9236-44)2005 Oct 15

15466864. Shcherbik N, Kee Y, Lyon N, Huibregtse JM, Haines DS, A single PXY motif located within the carboxyl terminus of Spt23p and Mga2p mediates a physical and functional interaction with ubiquitin ligase Rsp5p. J Biol Chem 279:51(53892-8)2004 Dec 17

15352157. Shcherbik N, Haines DS, Ub on the move. J Cell Biochem 93:1(11-9)2004 Sep 1

12867034. Shcherbik N, Zoladek T, Nickels JT, Haines DS, Rsp5p is required for ER bound Mga2p120 polyubiquitination and release of the processed/tethered transactivator Mga2p90. Curr Biol 13:14(1227-33)2003 Jul 15

12861003. Garriga J, Bhattacharya S, Calbó J, Marshall RM, Truongcao M, Haines DS, Graña X, CDK9 is constitutively expressed throughout the cell cycle, and its steady-state expression is independent of SKP2. Mol Cell Biol 23:15(5165-73)2003 Aug

12717421. Bhattacharya S, Garriga J, Calbó J, Yong T, Haines DS, Graña X, SKP2 associates with p130 and accelerates p130 ubiquitylation and degradation in human cells. Oncogene 22:16(2443-51)2003 Apr 24

11870222. Shcherbik N, Kumar S, Haines DS, Substrate proteolysis is inhibited by dominant-negative Nedd4 and Rsp5 mutants harboring alterations in WW domain 1. J Cell Sci 115:Pt 5(1041-8)2002 Mar 1

10871862. Pan Y, Haines DS, Identification of a tumor-derived p53 mutant with novel transactivating selectivity. Oncogene 19:27(3095-100)2000 Jun 22

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