748 Moll R, Franke WW, Schiller DL, Geiger B, Krepler R (1982) The cat- alog of human cytokeratins: patterns of expression in normal epi- thelia, tumors and cultured cells. Cell 31:11–24 Moscat J, Diaz-Meco MT, Wooten MW (2007) Signal integration and diversiWcation through the p62 scaVold protein. Trends Biochem Sci 32:95–100 Müller T, Langner C, Fuchsbichler A, Heinz-Erian P, Ellemunter H, Schlenck B, Bavdekar AR, Pradhan AM, Pandit A, Müller-Hoc- ker J, Melter M, Kobayashi K, Nagasaka H, Kikuta H, Müller W, Tanner MS, Sternlieb I, Zatloukal K, Denk H (2004) Immunohis- tochemical analysis of Mallory bodies in Wilsonian and non-Wil- sonian hepatic copper toxicosis. Hepatology 39:963–969 Nakamichi I, Hatakeyama S, Nakayama KI (2002) Formation of Mal- lory body-like inclusions and cell death induced by deregulated expression of keratin 18. Mol Biol Cell 13:3441–3451 Nakamichi I, Toivola DM, Strnad P, Michie SA, Oshima RG, Bariba- ult H, Omary MB (2005) Keratin 8 overexpression promotes mouse Mallory body formation. J Cell Biol 171:931–937 Nan L, Dedes J, French BA, Bardag-Gorce F, Li J, Wu Y, French SW (2006) Mallory body (cytokeratin aggresomes) formation is pre- vented in vitro by p38 inhibitor. Exp Mol Pathol 80:228–240 Nezis IP, Simonsen A, Sagona AP, Finley K, Gaumer S, Contamine D, Rusten TE, Stenmark H, Brech A (2008) Ref(2) P, the Drosophila melanogaster homologue of mammalian p62, is required for the formation of protein aggregates in adult brain. J Cell Biol 180:1065–1071 Omary MB, Ku NO, Liao J, Price D (1998) Keratin modiWcations and solubility properties in epithelial cells and in vitro. Subcell Bio- chem 31:105–140 Omary MB, Ku NO, Toivola DM (2002) Keratins: guardians of the liv- er. Hepatology 35:251–257 Omary MB, Coulombe PA, McLean WHI (2004) Mechanism of dis- ease. Intermediate Wlament proteins and their associated diseases. N Engl J Med 351:2087–2100 Omary MB, Ku NO, Tao GZ, Toivola DM, Liao J (2006) “Heads and tails” of intermediate Wlament phosphorylation: multiple sites and functional insights. Trends Biochem Sci 31:383–394 Orrego H, Blake JE, Blendis LM, Medline A (1987) Prognosis of alco- holic cirrhosis in the presence and absence of alcoholic hepatitis. Gastroenterology 92:208–214 Oshima RG (2002) Apoptosis and keratin intermediate Wlaments. Cell Death DiVer 9:486–492 Owens DW, Wilson NJ, Hill AJ, Rugg EL, Porter RM, Hutcheson AM, Quinlan RA, van Heel D, Parkes M, Jewell DP, Campbell SS, Ghosh S, Satsangi J, Lane EB (2004) Human keratin 8 mutations that disturb Wlament assembly observed in inXammatory bowel disease patients. J Cell Sci 117:1989–1999 Owens DW, Lane EB (2004) Keratin mutations and intestinal pathol- ogy. J Pathol 204:377–385 Pallari HM, Eriksson JE (2006) Intermediate Wlaments as signaling platforms. Sci STKE 19:pe53 Parola M, Robino G (2001) Oxidative stress-related molecules and liv- er Wbrosis. J Hepatol 35:297–306 Pekny M, Pekna M (2004) Astrocyte intermediate Wlaments in CNS pathologies and regeneration. J Pathol 204:428–437 Pessayre D (2007) Role of mitochondria in non-alcoholic fatty liver disease. J Gastroenterol Hepatol 22:S20–S27 Ramesh Babu J, Lamar Seibenhener M, Peng J, Strom AL, Kemppai- nen R, Cox N, Zhu H, Wooten MC, Diaz-Meco MT, Moscat J, Wooten MW (2007) Genetic inactivation of p62 leads to accumu- lation of hyperphosphorylated tau and neurodegeneration. J Neu- rochem in press Ray MB (1987) Distribution patterns of cytokeratin antigen determi- nants in alcoholic and nonalcoholic liver diseases. Hum Pathol 18:61–66 123 Histochem Cell Biol (2008) 129:735–749 Riley NE, Li J, Worrall S, Rothnagel JA, Swagell C, van Leeuwen FW, French SW (2002) The Mallory body as an aggresome: in vitro studies. Exp Mol Pathol 72:17–23 Riley NE, Li J, McPhaul LW, Bardag-Gorce F, Lue YH, French SW (2003) Heat shock proteins are present in Mallory bodies (cyto- keratin aggresomes) in human liver biopsy specimens. Exp Mol Pathol 74:168–172 Ross CA, Poirier MA (2004) Protein aggregation and neurodegenera- tive disease. Nat Med 10:S10–S17 Schalinske KL, Nieman KM (2005) Disruption of methyl group metabolism by ethanol. Nutr Rev 63:387–391 Schweizer J, Bowden PE, Coulombe PA, Langbein L, Lane EB, Magin TM, Maltais L, Omary MB, Parry DA, Rogers MA, Wright MW (2006) New consensus nomenclature for mammalian keratins. J Cell Biol 174:169–174 Seibenhener ML, Babu JR, Geetha T, Wong HC, Krishna NR, Wooten MW (2004) Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation. Mol Cell Biol 24:8055–8068 Shin J (1998) P62 and the sequestosome, a novel mechanism for pro- tein metabolism. Arch Pharm Res 21:629–633 Smith RA, Porteous CM, Gane AM, Murphy MP (2003) Delivery of bioactive molecules to mitochondria in vivo. Proc Natl Acad Sci U S A 100:5407–54012 Stenoien DL, Cummings CJ, Adams HP, Mancini MG, Patel K, De- Martino GN, Marcelli M, Weigel NL, Mancini MA (1999) Poly- glutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC– 1, and are suppressed by the HDJ-2 chaperone. Hum Mol Genet 8:731–741 Stone MR, O’Neill A, Lovering RM, Strong J, Resneck WG, Reed PW, Toivola DM, Ursitti JA, Omary MB, Bloch RJ (2007) Ab- sence of keratin 19 in mice causes skeletal myopathy with mito- chondrial and sarcolemmal reorganization. J Cell Sci 120:3999– 4008 Strnad P, Lienau TC, Tao GZ, Lazzeroni LC, Stickel F, Schuppan D, Omary MB (2006) Keratin variants associate with progression of Wbrosis during chronic hepatitis C infection. Hepatology 43:1354–1363 Strnad P, Harada M, Siegel M, Terkeltaub RA, Graham RM, Khosla C, Omary MB (2007) Transglutminase-2 regulates Mallory body inclusion formation and injury associated liver hypertrophy. Gas- troenterology 132:1515–1526 Strnad P, Tao GZ, Zhou Q, Harada M, Toivola DM, Brunt EM, Omary MB (2008) Keratin mutation predisposes to mouse liver Wbrosis and unmasks diVerential eVects of the carbon tetrachloride and thioacetamide models. Gastroenterology 134:1169–1179 Strnad P, Tao GZ, So P, Lau K, Schilling J, Wei Y, Liao J, Omary MB “Toxic memory” via chaperone modiWcation is a potential mech- anism for rapid Mallory-Denk body induction. Hepatology sub- mitted Stumptner C, Heid H, Fuchsbichler A, Hauser H, Mischinger HJ, Zat- loukal K, Denk H (1999) Analysis of intracytoplasmic hyaline bodies in a hepatocellular carcinoma. Demonstration of p62 as major constituent. Am J Pathol 154:1701–1710 Stumptner C, Omary MB, Fickert P, Denk H, Zatloukal K (2000) Hepatocyte cytokeratins are hyperphosphorylated at multiple sites in human alcoholic hepatitis and in a Mallory body mouse model. Am J Pathol 156:77–90 Stumptner C, Fuchsbichler A, Heid H, Zatloukal K, Denk H (2002) Mallory body—a disease associated type of sequestosome. Hepa- tology 35:1053–1062 Stumptner C, Fuchsbichler A, Zatloukal K, Denk H (2007) In vitro production of Mallory bodies and intracellular hyaline bodies: the central role of sequestosome 1/p62. Hepatology 46:851–860