Disease relevance of KIN

• By recloning the cDNA into an appropriate vector, we produced kin17 protein in E. coli, purified it partially and shown that kin17 protein binds to double-stranded DNA [1].
• Among 16 cell lines, the highest KIN17 protein level was observed in H1299 non-small cell lung cancer cells, whereas the lowest was detected in MeWo melanoma cells [2].

High impact information on KIN

• However, in human cells derived from XPA or XPC patients the UVC-induced accumulation of KIN17 RNA and protein is abolished [3].
• Our results indicate that the presence of functional XPA and XPC proteins is essential for the up-regulation of the KIN17 gene after UVC irradiation [3].
• Global genome repair is required to activate KIN17, a UVC-responsive gene involved in DNA replication [3].
• They also show that the integrity of global genome repair is required to trigger KIN17 gene expression and probably other UVC-responsive genes [3].
• The human stress-activated protein kin17 belongs to the multiprotein DNA replication complex and associates in vivo with mammalian replication origins [4].

Biological context of KIN

• The human stress-activated protein kin17 accumulates in the nuclei of proliferating cells with predominant colocalization with sites of active DNA replication [4].
• We demonstrated here that kin17 protein strongly associates in vivo with DNA fragments containing replication origins in both human HeLa and monkey CV-1 cells [4].
• In addition, the association of kin17 protein to DNA fragments containing replication origins was also analyzed as a function of the cell cycle [4].
• High binding of kin17 protein was found at the G(1)/S border and throughout the S phase and was negligible in both G(0) and M phases [4].
• Cells unable to repair UVC-induced DNA damage responded to lower doses of UVC with an even greater accumulation of c-fos and Kin17 mRNAs than repair-proficient wild-type cells, suggesting that a process in which a repair protein is involved regulates mRNA stability [5].

Anatomical context of KIN

• The Homo sapiens kin17 ((HSA)kin17) protein is a chromatin-associated protein conserved during evolution and overproduced in certain human tumor cell lines [6].
• The distribution of kin17 protein is in equilibrium between chromatin-DNA and the nuclear matrix [4].
• A two-step chromatographic fractionation of nuclear extracts from HeLa cells revealed that kin17 protein localized in vivo in distinct protein complexes of high molecular weight [4].
• We observed that certain carcinoma cell lines also up-regulated kin17 protein, suggesting that increased kin17 protein levels may be a consequence of the immortalized phenotype [7].
• Herein, we show that human fibroblasts (MRC5-V2 and CHSV4) immortalized with SV40 overexpress endogenous kin17 protein, as compared with normal diploid human fibroblasts [7].

Associations of KIN with chemical compounds

• Kin17 gene encodes a 45 kDa protein which binds to DNA and presents a limited similarity with a functional domain of the bacterial RecA protein [8].
• After L-mimosine block and withdrawal we observed that kin17 protein was recruited in the nucleus during re-entry and progression through S phase [9].
• In the presence of DNA damage in S phase cells, the distribution of kin17 protein became mainly associated with chromosomal DNA, as judged by limited formaldehyde cross-linking of living cells [9].
• A Tandem of SH3-like Domains Participates in RNA Binding in KIN17, a Human Protein Activated in Response to Genotoxics [10].
• NMR Assignment of Region 51-160 of Human KIN17, a DNA and RNA-binding Protein [11].

Regulatory relationships of KIN

• Using expression vectors, we show that overexpression of kin17 protein inhibits cell-cycle progression into S phase [8].

Other interactions of KIN

• Identification of KIN (KIN17), a human gene encoding a nuclear DNA-binding protein, as a novel component of the TP53-independent response to ionizing radiation [12].
• The human KIN (also known as KIN17) gene encodes a 45-kDa nuclear DNA-binding protein that participates in the response to UVC radiation and is immunologically related to the bacterial RecA protein [12].
• Cells displaying higher KIN17 protein levels exhibited elevated RPA70 protein contents [2].

Analytical, diagnostic and therapeutic context of KIN

• KIN17 mRNA is highly expressed in rodent transformed AtT-20 neuroendocrine cells whereas it can be detected only in the total RNA of mouse embryos and various normal adult tissues by reverse transcription and PCR amplification [1].
• Molecular cloning and characterization of the human KIN17 cDNA encoding a component of the UVC response that is conserved among metazoans [13].
• Flow cytometry analysis revealed that 48 h after transfection the uppermost KIN17-positive RKO cells shifted in the cell cycle toward higher DNA content, suggesting that KIN17 protein induced defects in chromatin conformation [2].
• Crystallization and halide phasing of the C-terminal domain of human KIN17 [14].
• The physical interaction of kin17 protein with components of the nuclear matrix was confirmed and visualized by indirect immunofluorescence and immunoelectron microscopy [9].

References