39-442: White Cat may refer to: Deaf white cat , domestic cats with a pure white coat who suffer from congenital deafness The White Cat (fairy tale) , French fairy tale by Madame d'Aulnoy White Cat (book) , 2010 book by Holly Black Black Cat, White Cat , 1998 Yugoslav romantic comedy film White Cat Black Cat , Hong Kong children's comic book series The White Cat (film) ,
78-447: A microarray study (which confirmed the above targets) include the following, The LysRS -Ap 4 A-MITF signaling pathway was first discovered in mast cells , in which, the A mitogen-activated protein kinase (MAPK) pathway is activated upon allergen stimulation. The binding of immunoglobulin E to the high-affinity IgE receptor ( FcεRI ) provides the stimulus that starts the cascade. Lysyl- tRNA synthetase (LysRS) normally resides in
117-664: A 1950 Swedish drama film directed by Hasse Ekman Victoria the White Cat , a character from the 1981 musical Cats Ora White Cat , a battery electric city car Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title White Cat . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=White_Cat&oldid=1120419075 " Category : Disambiguation pages Hidden categories: Short description
156-453: A syndrome of hearing loss and depigmentation caused by a genetic disruption to neural crest cell development, such a disruption would lead to this presentation in cats as well. Waardenburg syndrome type 2A (caused by a mutation in MITF ) has been found in many other small mammals including dogs, minks and mice, and they all display at least patchy white depigmentation and some degeneration of
195-474: A synergistic transactivation of the dopachrome tautomerase gene promoter, which is an early melanoblast marker. LEF-1 is involved in the process of regulation by Wnt signaling. LEF-1 also cooperates with MITF-related proteins like TFE3. MITF is a modulator of LEF-1, and this regulation ensures efficient propagation of Wnt signals in many cells. Translational regulation of MITF is still an unexplored area with only two peer-reviewed papers (as of 2019) highlighting
234-402: A white coat despite the underlying pattern/colour. A cat that lacks this dominant masking gene (ww) will exhibit a coat colour/pattern. KIT mutations have also led to patchy depigmentation and different coloured irises in humans, and KIT has been found to increase MITF expression, the gene involved in human Waardenburg syndrome type 2A. The established link between deafness and blue eyes
273-475: Is a protein that in humans is encoded by the MITF gene . MITF is a basic helix-loop-helix leucine zipper transcription factor involved in lineage-specific pathway regulation of many types of cells including melanocytes , osteoclasts , and mast cells . The term "lineage-specific", since it relates to MITF, means genes or traits that are only found in a certain cell type. Therefore, MITF may be involved in
312-509: Is a rare genetic disorder. Its symptoms include deafness, minor defects, and abnormalities in pigmentation. Mutations in the MITF gene have been found in certain patients with Waardenburg syndrome, type II. Mutations that change the amino acid sequence of that result in an abnormally small MITF are found. These mutations disrupt dimer formation, and as a result cause insufficient development of melanocytes. The shortage of melanocytes causes some of
351-492: Is a transcriptional inhibitor that acts by inhibiting STAT3 's DNA binding activity. PIAS3 directly interacts with MITF, and STAT3 does not interfere with the interaction between PIAS3 and MITF. PIAS3 functions as a key molecule in suppressing the transcriptional activity of MITF. This is important when considering mast cell and melanocyte development. MITF, TFE3 and TFEB are part of the basic helix-loop-helix-leucine zipper family of transcription factors. Each protein encoded by
390-415: Is a ubiquitin conjugating enzyme whose proteins associates with MITF. Although hUBC9 is known to act preferentially with SENTRIN/SUMO1, an in vitro analysis demonstrated greater actual association with MITF. hUBC9 is a critical regulator of melanocyte differentiation. To do this, it targets MITF for proteasome degradation. Protein kinase C-interacting protein 1 (PKC1) associates with MITF. Their association
429-461: Is also an integral part of melanocytes, where it regulates the expression of a number of proteins with melanogenic potential. Continuous expression of MITF at a certain level is one of the necessary factors for melanoma cells to proliferate, survive and avoid detection by host immune cells through the T-cell recognition of the melanoma-associated antigen (melan-A). Post-translational modifications of
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#1732793408288468-496: Is also known to play a crucial role in melanoma progression. Since it is a transcription factor that is involved in the regulation of genes related to invasiveness, migration, and metastasis, it can play a role in the progression of melanoma. MITF recognizes E-box (CAYRTG) and M-box (TCAYRTG or CAYRTGA) sequences in the promoter regions of target genes. Known target genes (confirmed by at least two independent sources) of this transcription factor include, Additional genes identified by
507-440: Is altered. A reduced number of melanocytes can lead to hearing loss, and decreased melanin production can account for the light skin and hair color that make Tietz syndrome so noticeable. Melanocytes are commonly known as cells that are responsible for producing the pigment melanin which gives coloration to the hair, skin, and nails. The exact mechanisms of how exactly melanocytes become cancerous are relatively unclear, but there
546-565: Is conserved across vertebrates, including in fishes such as zebrafish and Xiphophorus . An understanding of MITF is necessary to understand how certain lineage-specific cancers and other diseases progress. In addition, current and future research can lead to potential avenues to target this transcription factor mechanism for cancer prevention. As mentioned above, changes in MITF can result in serious health conditions. For example, mutations of MITF have been implicated in both Waardenburg syndrome and Tietz syndrome . Waardenburg syndrome
585-511: Is different from Wikidata All article disambiguation pages All disambiguation pages Deaf white cat Congenital sensorineural deafness occurs commonly in domestic cats with a white coat. It is a congenital deafness caused by a degeneration of the inner ear . Deafness is far more common in white cats than in those with other coat colours. Domesticated cats with blue eyes and white coats are often completely deaf. Charles Darwin mentions this phenomenon in his book, On
624-692: Is found in the link between deafness, blue eyes and solid white coats. However, it is a common misconception that all white cats with blue eyes are deaf. It is possible to have a cat with a naturally white coat without this gene, as an extreme form of white spotting , although this is rare – some small non-white patch usually remains. Furthermore, there are multiple different genes responsible for blue (incl. odd) eyes, and several of these genes are not linked to masking, white coats or deafness (e.g., " Siamese " colourpoint-gene , Ojos Azules -gene, etc.). For example, solid white blue-eyed Foreign White or Ojos Azules cats are not linked to deafness. Deafness depends on
663-510: Is induced by the presence of the KIT oncogenic mutation D816V. This KIT pathway is dependent on SRC protein family activation signaling. The induction of serine phosphorylation by the frequently altered MAPK/BRAF pathway and the GSK-3 pathway in melanoma regulates MITF nuclear export and thereby decreasing MITF activity in the nucleus. Similarly, tyrosine phosphorylation mediated by the presence of
702-588: Is ongoing research to gain more information about the process. For example, it has been uncovered that the DNA of certain genes is often damaged in melanoma cells, most likely as a result of damage from UV radiation, and in turn increases the likelihood of developing melanoma. Specifically, it has been found that a large percentage of melanomas have mutations in the B-RAF gene which leads to melanoma by causing an MEK-ERK kinase cascade when activated. In addition to B-RAF, MITF
741-429: Is reduced upon cell activation. When this happens MITF disengages from PKC1. PKC1 by itself, found in the cytosol and nucleus, has no known physiological function. It does, however, have the ability to suppress MITF transcriptional activity and can function as an in vivo negative regulator of MITF induced transcriptional activity. The functional cooperation between MITF and the lymphoid enhancing factor (LEF-1) results in
780-595: The mi locus in mice, and its protumorogenic targets include factors involved in cell death, DNA replication , repair, mitosis, microRNA production, membrane trafficking, mitochondrial metabolism, and much more. Mutation of this gene results in deafness, bone loss, small eyes, and poorly pigmented eyes and skin. In human subjects, because it is known that MITF controls the expression of various genes that are essential for normal melanin synthesis in melanocytes, mutations of MITF can lead to diseases such as melanoma , Waardenburg syndrome , and Tietz syndrome . Its function
819-503: The HINT1 molecules have been shown to affect MITF gene expression as well as the binding of Ap4A. Mutations in HINT1 itself have been shown to be the cause of axonal neuropathies . The regulatory mechanism relies on the enzyme diadenosine tetraphosphate hydrolase, a member of the Nudix type 2 enzymatic family (NUDT2), to cleave Ap4A, allow the binding of HINT1 to MITF and thus suppress
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#1732793408288858-434: The KIT oncogenic mutation D816V also increases the presence of MITF in the cytoplasm. Most transcription factors function in cooperation with other factors by protein–protein interactions . Association of MITF with other proteins is a critical step in the regulation of MITF-mediated transcriptional activity. Some commonly studied MITF interactions include those with MAZR, PIAS3 , Tfe3 , hUBC9, PKC1, and LEF1 . Looking at
897-510: The Origin of Species , to explain correlated variation. Deafness can occur in white cats with yellow, green or blue irises, although it is mostly likely in white cats with blue irises. In white cats with mixed-coloured eyes ( odd-eyed cats ), it has been found that deafness is more likely to affect the ear on the blue-eyed side. Odd-eyed white cats have one blue eye and one yellow, amber, copper/orange or green coloured eye. Approximately 15–40% of
936-923: The cat's genotype (genetic make-up), and not its phenotype (physical appearance). Therefore, not all solid white cats with one or two blue eyes are deaf. It is not advisable to breed from deaf white cats, as this would pass the trait along. BAER-testing ( Brainstem Auditory Evoked Response ) is used to test deafness in cats. MITF 4C7N 4286 17342 ENSG00000187098 ENSMUSG00000035158 O75030 Q08874 NM_198159 NM_198177 NM_198178 NM_001354604 NM_001354605 NM_001354606 NM_001354607 NM_001354608 NM_001113198 NM_001178049 NM_008601 NP_937802 NP_937820 NP_937821 NP_001341533 NP_001341534 NP_001341535 NP_001341536 NP_001341537 NP_001106669 NP_001171520 NP_032627 Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32
975-454: The characteristic features of Waardenburg syndrome. Tietz syndrome, first described in 1923, is a congenital disorder often characterized by deafness and leucism. Tietz is caused by a mutation in the MITF gene. The mutation in MITF deletes or changes a single amino acid base pair specifically in the base motif region of the MITF protein. The new MITF protein is unable to bind to DNA and melanocyte development and subsequently melanin production
1014-439: The cochlea and saccule , as in deaf white cats. A major gene that causes a cat to have a white coat is a dominant masking gene, an allele of KIT which suppresses pigmentation and hearing. The cat would have an underlying coat colour and pattern, but when the dominant white gene is present, that pattern will not be expressed, and the cat will be deaf. A cat that is homozygous (WW) or heterozygous (Ww) for this gene will have
1053-517: The expression of the MITF transcribed genes. NUDT2 itself has also been shown to be associated with human breast carcinoma, where it promotes cellular proliferation. The enzyme is 17 kDa large and can freely diffuse between the nucleus and cytosol explaining its presence in the nucleus. It has also been shown to be actively transported into the nucleus by directly interacting with the N-terminal domain of importin-β upon immunological stimulation of
1092-407: The family of transcription factors can bind DNA. MITF is necessary for melanocyte and eye development and new research suggests that TFE3 is also required for osteoclast development, a function redundant of MITF. The combined loss of both genes results in severe osteopetrosis, pointing to an interaction between MITF and other members of its transcription factor family. In turn, TFEB has been termed as
1131-449: The importance. During glutamine starvation of melanoma cells ATF4 transcripts increases as well as the translation of the mRNA due to eIF2α phosphorylation. This chain of molecular events leads to two levels of MITF suppression: first, ATF4 protein binds and suppresses MITF transcription and second, eIF2α blocks MITF translation possibly through the inhibition of eIF2B by eIF2α. MITF can also be directly translationally modified by
1170-465: The inhibitory complex, allowing it to transcribe its target genes. Specifically, Ap4A causes a polymerization of the HINT1 molecule into filaments. The polymerization blocks the interface for MITF and thus prevents the binding of the two proteins. This mechanism is dependent on the precise length of the phosphate bridge in the Ap4A molecule so other nucleotides such as ATP or AMP will not affect it. MITF
1209-481: The mast cells. Growing evidence is pointing to the fact that the LysRS-Ap4A-MITF signalling pathway is in fact an integral aspect of controlling MITF transcriptional activity. Activation of the LysRS-Ap4A-MITF signalling pathway by isoproterenol has been confirmed in cardiomyocytes. A heart specific isoform of MITF is a major regulator of cardiac growth and hypertrophy responsible for heart growth and for
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1248-429: The master regulator of lysosome biogenesis and autophagy. Interestingly, MITF, TFEB and TFE3 separate roles in modulating starvation-induced autophagy have been described in melanoma. Moreover, MITF and TFEB proteins, directly regulate each other’s mRNA and protein expression while their subcellular localization and transcriptional activity are subject to similar modulation, such as the mTOR signaling pathway. UBC9
1287-403: The multisynthetase complex. This complex consists of nine different aminoacyl-tRNA synthetases and three scaffold proteins and has been termed the "signalosome" due to its non-catalytic signalling functions. After activation, LysRS is phosphorylated on Serine 207 in a MAPK-dependent manner. This phosphorylation causes LysRS to change its conformation, detach from the complex and translocate into
1326-488: The nucleus, where it associates with the encoding histidine triad nucleotide–binding protein 1 (HINT1) thus forming the MITF-HINT1 inhibitory complex. The conformational change also switches LysRS activity from aminoacylation of Lysine tRNA to diadenosine tetraphosphate (Ap4A) production. Ap4A, which is an adenosine joined to another adenosine through a 5‘-5’tetraphosphate bridge, binds to HINT1 and this releases MITF from
1365-466: The physiological response of the cardiomyocytes to beta-adrenergic stimulation. MITF is phosphorylated on several serine and tyrosine residues. Serine phosphorylation is regulated by several signaling pathways including MAPK/BRAF/ERK , receptor tyrosine kinase KIT , GSK-3 and mTOR . In addition, several kinases including PI3K , AKT , SRC and P38 are also critical activators of MITF phosphorylation. In contrast, tyrosine phosphorylation
1404-493: The rewiring of signaling cascades that are specifically required for the survival and physiological function of their normal cell precursors. MITF, together with transcription factor EB ( TFEB ), TFE3 and TFEC , belong to a subfamily of related bHLHZip proteins, termed the MiT-TFE family of transcription factors. The factors are able to form stable DNA-binding homo- and heterodimers. The gene that encodes for MITF resides at
1443-482: The solid white cats have one or two blue eyes. According to the ASPCA Complete Guide to Cats, "17 to 20 percent of white cats with non-blue eyes are deaf; 40 percent of "odd-eyed" white cats with one blue eye are deaf; and 65 to 85 percent of blue-eyed white cats are deaf." In one 1997 study of white cats, 72% of the animals were found to be totally deaf. The entire organ of Corti in the cochlea
1482-474: The variety of structures gives insight into MITF's varied roles in the cell. The Myc-associated zinc-finger protein related factor (MAZR) interacts with the Zip domain of MITF. When expressed together, both MAZR and MITF increase promoter activity of the mMCP-6 gene. MAZR and MITF together transactivate the mMCP-6 gene. MAZR also plays a role in the phenotypic expression of mast cells in association with MITF. PIAS3
1521-486: Was found to have degenerated in the first few weeks after birth; however, even during these weeks no brain stem responses could be evoked by auditory stimuli, suggesting that these animals had never experienced any auditory sensations. It was found that some months after the organ of Corti had degenerated, the spiral ganglion of the cochlea also began to degenerate. Although few studies have been done to link this to genes known to be involved in human Waardenburg syndrome ,
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