The expression and role of krüppel-like factor 4 in psoriasis.

BACKGROUND: Krüppel-like factor 4 (KLF4) is a transcription factor that regulates a diverse array of cellular processes, including development, differentiation, proliferation, and apoptosis. Although its function in keratinocytes has been widely studied, its exact role in psoriasis has not been elucidated. OBJECTIVE: We designed this study to investigate epidermal expression levels of KLF4 and the change in KLF4 expression after treatment in patients with psoriasis. METHODS: We compared the expression levels of KLF4 in the basal, suprabasal, and superficial epidermal layers, in psoriatic lesional, non-lesional, and normal skin, using an immunoreactivity intensity distribution index (IRIDI). In addition, we measured the change in KLF4 expression on the basis of the IRIDI and by reverse transcription polymerase chain reaction (RT-PCR) analysis after treatment. RESULTS: The combined IRIDI scores in psoriatic lesional skin were significantly higher than the scores in both non-lesional and normal skin. The psoriatic epidermis, particularly the suprabasal layer, showed a significantly increased IRIDI score compared to that of non-lesional and normal skin, which was significantly decreased after treatment. RT-PCR analysis exhibited a slight increase in KLF4 mRNA expression level after treatment; however, this increase was not significant. CONCLUSION: These data indicate that KLF4 could regulate epidermal proliferation and differentiation. Moreover, we believe that KLF4 may play an important role in the physiological reaction to counteract abnormal differentiation and proliferation of keratinocytes.

Structural insights into activation of the retinal L-type Ca²âº channel (Cav1.4) by Ca²âº-binding protein 4 (CaBP4).

CaBP4 modulates Ca(2+)-dependent activity of L-type voltage-gated Ca(2+) channels (Cav1.4) in retinal photoreceptor cells. Mg(2+) binds to the first and third EF-hands (EF1 and EF3), and Ca(2+) binds to EF1, EF3, and EF4 of CaBP4. Here we present NMR structures of CaBP4 in both Mg(2+)-bound and Ca(2+)-bound states and model the CaBP4 structural interaction with Cav1.4. CaBP4 contains an unstructured N-terminal region (residues 1-99) and four EF-hands in two separate lobes. The N-lobe consists of EF1 and EF2 in a closed conformation with either Mg(2+) or Ca(2+) bound at EF1. The C-lobe binds Ca(2+) at EF3 and EF4 and exhibits a Ca(2+)-induced closed-to-open transition like that of calmodulin. Exposed residues in Ca(2+)-bound CaBP4 (Phe(137), Glu(168), Leu(207), Phe(214), Met(251), Phe(264), and Leu(268)) make contacts with the IQ motif in Cav1.4, and the Cav1.4 mutant Y1595E strongly impairs binding to CaBP4. We conclude that CaBP4 forms a collapsed structure around the IQ motif in Cav1.4 that we suggest may promote channel activation by disrupting an interaction between IQ and the inhibitor of Ca(2+)-dependent inactivation domain.

¹H, ¹5N, and ¹³C chemical shift assignments of murine calcium-binding protein 4.

Calcium-binding protein 4 (CaBP4) regulates voltage-gated Ca(2+) channels in retinal rod cells and specific mutations within CaBP4 are associated with congenital stationary night blindness type 2. We report complete NMR chemical shift assignments of the Ca(2+)-saturated form of CaBP4 with Ca(2+) bound at EF1, EF3 and EF4 (BMRB no. 18877).

Mucinous nevus with fat: an unusual case report and literature review.

Mucinous nevus is a rare entity classified as either cutaneous mucinosis or connective tissue nevi. Clinically, multiple papules or plaques develop at birth or in early adulthood and grow to form verrucous or nevoid feature with a unilateral or often zosteriform distribution on the trunk. Histopathologically, it is characterized by mucin deposits localized in the papillary dermis, clearly distinguishing this entity from other types of cutaneous mucinosis. A 18-year-old male presented with multiple, skin-colored, pinhead to pea-sized, grouped, flat tapped, soft papules on the back. This skin lesion was found accidentally 3 years ago with no symptom. Histologic findings revealed an acanthotic epidermis with thin elongated rete ridges and orthohyperkeratosis. In papillary dermis, fine collagen fibers were interspersed in an abundant ground substance that stained positively with Alcian blue at pH2.5. Herein the authors describe an unusual case of mucinous nevus and review the relevant literature.

Nuclear magnetic resonance structure of calcium-binding protein 1 in a Ca(2+) -bound closed state: implications for target recognition.

Calcium-binding protein 1 (CaBP1), a neuron-specific member of the calmodulin (CaM) superfamily, regulates the Ca(2+) -dependent activity of inositol 1,4,5-triphosphate receptors (InsP3Rs) and various voltage-gated Ca(2+) channels. Here, we present the NMR structure of full-length CaBP1 with Ca(2+) bound at the first, third, and fourth EF-hands. A total of 1250 nuclear Overhauser effect distance measurements and 70 residual dipolar coupling restraints define the overall main chain structure with a root-mean-squared deviation of 0.54 Å (N-domain) and 0.48 Å (C-domain). The first 18 residues from the N-terminus in CaBP1 (located upstream of the first EF-hand) are structurally disordered and solvent exposed. The Ca(2+) -saturated CaBP1 structure contains two independent domains separated by a flexible central linker similar to that in calmodulin and troponin C. The N-domain structure of CaBP1 contains two EF-hands (EF1 and EF2), both in a closed conformation [interhelical angles = 129° (EF1) and 142° (EF2)]. The C-domain contains EF3 and EF4 in the familiar Ca(2+) -bound open conformation [interhelical angles = 105° (EF3) and 91° (EF4)]. Surprisingly, the N-domain adopts the same closed conformation in the presence or absence of Ca(2+) bound at EF1. The Ca(2+) -bound closed conformation of EF1 is reminiscent of Ca(2+) -bound EF-hands in a closed conformation found in cardiac troponin C and calpain. We propose that the Ca(2+) -bound closed conformation of EF1 in CaBP1 might undergo an induced-fit opening only in the presence of a specific target protein, and thus may help explain the highly specialized target binding by CaBP1.

The role of KLF4 in UVB-induced murine skin tumor development and its correlation with cyclin D1, p53, and p21(Waf1/Cip1) in epithelial tumors of the human skin.

The zinc-finger-type transcriptional factor KLF4 is expressed in a variety of tissues including skin. KLF4 can function as either a tumor suppressor or an oncogene, depending on the type of tissue in which it is expressed, by modulating the expression of various factors. To understand the role of KLF4 in human skin cancer and also to evaluate the expression of cyclin D1, p53, and p21(Waf1/Cip1) in relation to the expression of KLF4, we evaluated the pattern of KLF4 expression during UVB-induced skin tumor development in SKH-1 hairless mice and in human skin cancer. We also determined whether there are correlations between the expression of KLF4, cyclin D1, p53, and p21 and non-melanoma skin tumors. KLF4 expression was found in the basal layer of non-irradiated control murine skin. Chronic UVB irradiation caused a progressive decrease in KLF4 expression, which was substantially decreased in UVB-induced murine skin tumors. In human precancerous lesions, KLF4 expression was maintained in 64.3% of Bowen's disease samples and 90.0% of AK samples. In contrast, KLF4 expression was significantly reduced in human cancer lesions (p = 0.004). A positive correlation was found between the expression of KLF4 and p21(Waf1/Cip1) in AK, whereas there was a negative correlation between the expression of cyclin D1 and p21(Waf1/Cip1) in Bowen's disease. Thus, our results suggest that KLF4 may function as a tumor suppressor in the skin and that the deregulated expression of KLF4 in the context of p21(Waf1/Cip1) and cyclin D1 expression may be involved in skin tumorigenesis.

1H, 15N, and 13C chemical shift assignments of calcium-binding protein 1 with Ca2+ bound at EF1, EF3 and EF4.

Calcium-binding protein 1 (CaBP1) regulates inositol 1,4,5-trisphosphate receptors (InsP(3)Rs) and a variety of voltage-gated Ca(2+) channels in the brain. We report complete NMR chemical shift assignments of the Ca(2+)-saturated form of CaBP1 with Ca(2+) bound at EF1, EF3 and EF4 (residues 1-167, BMRB no. 16862).