Desquamin is an epidermal ribonuclease

Abstract

Desquamin is a glycoprotein that we have isolated from the upper granular layer and the stratum corneum of human epidermis; it is not ordinarily expressed in submerged cultures, whose terminal differentiation stops short of formation of these layers. The exogenous addition of desquamin to human cultured keratinocytes extended their maturation, and hematoxylin staining indicated a loss of cell nuclei. For confirmation, cultured cells were lysed in situ, and the nuclei were incubated with desquamin for several days, then stained with hematoxylin. Damage to the nuclei was evident: the nuclear inclusions remained intact, while the surrounding basophilic nuclear matrix was degraded. Desquamin was then tested directly for nuclease activity. Ribonuclease activity was determined by incubating desquamin with human epidermal total RNA and monitoring the dose-dependent disappearance of the 28S and 18S ribosomal RNA bands in an agarose/formaldehyde gel. On RNA-containing zymogels, we confirmed the RNase activity to be specific to desquamin. Using synthetic RNA homopolymers, we found the active RNase domains to be limited to cytosine residues. On the contrary, DNA was not degraded by an analogous procedure, even after strand-separation by denaturation.

Death penalty for keratinocytes: apoptosis versus cornification

“…It has been suggested that desquamin is involved in the degradation of the nuclear matrix. 36 Cathepsin L2 is secreted in the intercellular space and probably participates in the desquamation event Similarities between both processes may lay in the fact that some proteins such as calpains, cathepsins, transglutaminases and transcription factors such as NF-kB and p53 family members participate in both signal transduction pathways (Figure 4). However, profound differences can be found at several levels: (1) p53, a major integrator of nuclear damageinduced cell death, has no obvious role in epidermal differentiation, while for terminal keratinocyte differentiation p63 is crucial; (2) caspases, the key regulators of apoptosis initiation and excecution, apparently play no role in adult keratinocyte differentiation, except maybe for the nonapoptotic caspase-14; (3) cathepsin L and C are implicated in hair follicle development and epidermal differentiation, while cathepsin B-deficient mice show impaired TNF-induced apoptosis in the liver but present no apparent skin phenotype; (4) transglutaminases I, III and V participate in the formation of cornified envelopes, whereas TG2 may contribute to apoptosis and (5) NF-kB protects most cell types, including keratinocytes, from apoptosis.…”

“…Desquamin, originally discovered as a lectin-like protein, is expressed in the transition zone between the granular and cornified layer. 35 Desquamin is able to degrade isolated nuclei, 36 leaving nuclear inclusions intact while degrading the surrounding basophilic nuclear matrix. This could make the DNA more prone to DNAse activity in cells.…”

Mitochondrial DNA mutations in human cancer

“…(Nagy et al, 2002). Loss of mtDNA and the mRNA coding for NADH dehydrogenase subunit 3 was reported in eight of 13 tumor kidney tissues in another study (Selvanayagam and Rajaraman, 1996). Moreover, PCR was used to study 39 human renal cell carcinomas (RCC) and matched normal kidney tissue removed during radical nephrectomy.…”

Mitochondria and Human Cancer

“…and duplications in other parts of the mitochondrial genome have been noted in a variety of human cancers including ovarian, thyroid, salivary, kidney, liver lung, colon, gastric brain, bladder, head and neck, prostate, and breast cancer, and leukemia . For example, a 40 bp insertion localized in the COX I gene appears to be specific for renal cell oncocytoma [74], and a deletion mutation resulting in the loss of mtDNA within NADH dehydrogenase subunit III is associated with renal carcinoma [80]. In a recent population based study involving 260 prostate cancer patients of European and AfricanAmerican descent and 54 benign controls without cancer, the frequency of COX I missense mutations was found to be significantly higher in prostate cancer patients compared to the no-cancer controls (12% vs. 1.9%, respectively).…”