COMMENTARY 1608 Journal of Investigative Dermatology (2009), Volume 129 Patel HP, Diaz LA, Anhalt GJ, Labib RS, Takahashi Y (1984) Demonstration of pemphigus antibodies on the cell surface of murine epidermal cell monolayers and their internalization. J Invest Dermatol 83:409–15 Sato M, Aoyama Y, Kitajima Y (2000) Assembly pathway of desmoglein 3 to desmosomes and its perturbation by pemphigus vulgaris-IgG in cultured keratinocytes, as revealed by time- lapsed labeling immunoelectron microscopy. Lab Invest 80:1583–92 Seishima M, Esaki C, Osada K, Mori S, Hashimoto T, Kitajima Y (1995) Pemphigus IgG, but not bullous pemphigoid IgG, causes a transient increase in intracellular calcium and inositol 1,4,5-triphosphate in DJM-1 cells, a squamous cell carcinoma line. J Invest Dermatol 104:33–7 Waschke J, Bruggeman P, Baumgartner W, Zillikens D, Drenckhahn D (2005) Pemphigus foliaceus IgG causes dissociation of desmoglein 1-containing junctions without blocking desmoglein 1 transinteraction. J Clin Invest 115:3157–65 Waschke J, Spindler V, Bruggeman P, Zillikens D, Schmidt G, Drenckhahn D (2006) Inhibition of Rho A activity causes pemphigus skin blistering. J Cell Biol 175:721–7 endocytosis and desmosome disassembly are coordinated responses to pemphigus autoantibodies. J Biol Chem 281:7623–34 Delva E, Jennings JM, Calkins CC, Kottke MD, Faundez V, Kowalczyk AP (2008) Pemphigus vulgaris IgG-induced desmoglein-3 endocytosis and desmosomal disassembly are mediated by a clathrin- and dynamin-independent mechanism. J Biol Chem 283:18303–13 Ihrie RA, Marques MR, Nguyen BT, Horner JS, Papazoglu C, Bronson RT et al. (2005) Perp is a p63-regulated gene essential for epithelial integrity. Cell 120:843–56 Mao X, Choi EJ, Payne AS (2009) Disruption of desmosome assembly by monovalent human pemphigus vulgaris monoclonal antibodies. J Invest Dermatol 129:908–18 Marques MR, Ihrie RA, Horner JS, Attardi LD (2006) The requirement for perp in postnatal viability and epithelial integrity reflects an intrinsic role in stratified epithelia. J Invest Dermatol 126:69–73 Nguyen B, Dusek RL, Beaudry VG, Marinkovich MP, Attardi LD (2009) Loss of the desmosomal protein Perp enhances the phenotypic effects of pemphigus vulgaris autoantibodies. J Invest Dermatol 129:1710–8 desmosomes to the effects of pem- phigus IgG. For example, agents that increase cell–cell adhesion may abro- gate the acantholytic effects of pemphi- gus IgG. One can envision at least two classes of intracellular events: (i) those that are directly activated by pemphigus IgG and that may represent part of the mechanism by which acantholysis pro- ceeds and (ii) those that regulate adhe- sion but are not directly activated by pemphigus IgG. Although distinguishing between these two classes of events will be important to defining in detail the mechanism of pemphigus IgG–induced acantholysis, both classes of events are likely to provide valid therapeutic tar- gets for treating this disorder. CONFLICT OF INTEREST The authors state no conflict of interest. ACKOWLEDGMENTS This work was supported by National Institutes of Health grant RO1 AI49427 (to DSR). REFERENCES Aoyama Y, Kitajima Y (1999) Pemphigus vulgaris– IgG causes a rapid depletion of desmoglein 3 (Dsg3) from the Triton X-100 soluble pools, leading to the formation of Dsg3-depleted desmosomes in a human squamous carcinoma cell line, DJM-1 cells. J Invest Dermatol 112:67–71 Aoyama Y, Owada MK, Kitajima Y (1999) A pathogenic autoantibody, pemphigus vulgaris- IgG, induces phosphorylation of desmoglein 3, and its dissociation from plakoglobin in cultured keratinocytes. Eur J Immunol 29:2233–40 Attardi LD, Reczek EE, Cosmas C, Demicco EG, McCurrach ME, Lowe SW et al. (2000) PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family. Genes Dev 14:704–18 Berkowitz P, Hu P, Liu Z, Diaz LA, Enghild JJ, Chua MP et al. (2005) Desmosome Signaling: inhibition of p38MAPK prevents pemphigus vulgaris IgG-induced cytoskeleton reorganization. J Biol Chem 280:23778–84 Berkowitz P, Hu P, Warren S, Liu Z, Diaz LA, Rubenstein DS (2006) p38MAPK inhibition prevents disease in pemphigus vulgaris mice. Proc Natl Acad Sci USA 103:12855–60 Berkowitz P, Chua M, Liu Z, Diaz LA, Rubenstein DS (2008) Autoantibodies in the autoimmune disease pemphigus foliaceus induce blistering via p38 mitogen-activated protein kinase- dependent signaling in the skin. Am J Pathol 173:1628–36 Caldelari R, de Bruin A, Baumann D, Suter MM, Bierkamp C, Balmer V et al. (2001) A central role for the armadillo protein plakoglobin in the autoimmune disease pemphigus vulgaris. J Cell Biol 153:823–34 Calkins CC, Setzer SV, Jennings JM, Summers S, Tsunoda K, Amagai M et al. (2006) Desmoglein See related article on pg 1769 UVB and UVA Initiate Different Pathways to p53-Dependent Apoptosis in Melanocytes Frances P. Noonan 1 and Edward C. De Fabo 1 The incidence of cutaneous malignant melanoma (CMM) has more than dou- bled in the past 25 years and continues to increase at over 3% per year across all age groups (Linos et al., this issue), and invasive and disseminated mela- noma in young women has increased by almost 10% since 1992 (Purdue et al., 2008). Early detection and excision of CMM can result in successful treatment, but disseminated disease is resistant to current therapies and has a very poor prognosis (Garbe and Eigentler, 2007). Sunlight exposure is a major risk fac- tor for melanoma. In this issue, Waster and Öllinger investigate the effects of UVB and UVA on melanocytes. Journal of Investigative Dermatology (2009) 129, 1608–1610. doi:10.1038/jid.2009.116 Abundant epidemiologic evidence exists that cutaneous malignant mela- noma (CMM) is associated with expo- sure to sunlight—most likely to its UV component (reviewed in Tucker, 2008). Human populations of similar genetic origin have a greater risk of mela- noma when they reside in locations 1 Department of Microbiology, Immunology, and Tropical Medicine, George Washington University Medical Center, Washington, DC, USA Correspondence: Dr Frances P. Noonan, Department of Microbiology, Immunology, and Tropical Medicine, George Washington University Medical Center, 2300 Eye Street NW, Ross Hall, Room 113, Washington, DC 20037, USA. E-mail: drmfpn@gwumc.edu