Disease relevance of MLC1

• Note there are 2 genes called MLC1. Seemingly half the information in this page refers to the wrong gene - for myosin light chain 1 (Myl1). Some disambiguation necessary.

• BACKGROUND/AIMS: We screened a novel gene MLC1 in human liver cancer tissue by differential display, and its cDNA full-length is 1600bp [1]. Wrong gene?
• 1. CONCLUSIONS: MLC1 gene showed up-regulation expression at both the mRNA and protein levels in HCC tissues and that MLC1 plays an important role in the growth of hepatoma cell SMMC7721 in vitro and vivo [1]. Wrong gene?
• Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disorder characterized by macrocephaly, deterioration of motor functions with ataxia, and spasticity, eventuating in mental decline [2].
• Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a progressive inherited neurological disorder characterized by macrocephaly, deterioration in motor functions and cerebellar ataxia [3].
• In conclusion MLC-1 cannot be used as a diagnostic marker in differential diagnosis of dyspnea [4]. Wrong gene - also known as Myl1.

Psychiatry related information on MLC1

• A missense mutation in MLC1 (putative cation-channel gene on 22q13) co-segregating with periodic catatonic schizophrenia has been reported [5].
• MLC1 gene is associated with schizophrenia and bipolar disorder in Southern India [5].
• We report here that a Leu309Met mutation in WKL1, a positional candidate gene on chromosome 22q13.33 encoding a putative non-selective cation channel expressed exclusively in brain, co-segregates with periodic catatonia in an extended pedigree [6].
• Murine A/J anti-p-azophenylarsonate mAb that express a dominant cross-reactive Id are encoded by a single set of germ-line VH and VL region genes [7]. Wrong gene.
• The missense mutation in the WKL1 gene not found in patients with bipolar affective disorder [8].

High impact information on MLC1

• Somatic diversification of chicken V gene segments occurs by intrachromosomal gene conversion, a DNA recombination process which involves unidirectional transfer of nucleotide sequence blocks from families of V region pseudogenes into the functional rearranged VH and VL genes [9]. Wrong gene.
• Ca2+ sensitivity of smooth muscle and nonmuscle myosin II reflects the ratio of activities of myosin light-chain kinase (MLCK) to myosin light-chain phosphatase (MLCP) and is a major, regulated determinant of numerous cellular processes [10]. Wrong gene.
• Whereas sequences proximal to the two MLC promoters do not appear to contain tissue-specific regulatory elements, a 0.9-kb DNA segment, located greater than 24 kb downstream of the MLC1 promoter, dramatically increases CAT gene expression in differentiated myotubes but not in undifferentiated myoblasts or nonmuscle cells [11].
• To define DNA sequences involved in MLC transcriptional control, we constructed a series of plasmid vectors in which segments of the rat MLC locus were linked to a CAT gene and assayed for expression in muscle and nonmuscle cells [11].
• Thus, it follows that identification of regulatory factors involved in MLC phosphorylation should elucidate the nature of spindle-derived regulatory signals and lead to a model for how they control cytokinesis [12].

Chemical compound and disease context of MLC1

• Functional analysis of the unreactive (TH1-) and reactive (TH1+) T-cell subclasses demonstrated that TH1- cells mounted a good proliferative response to a battery of specific soluble antigens (mumps, PPD, tetanus toxoid) but neither responded in MLC, nor elaborated LMF in response to tetanus toxoid [13].
• We studied the separate contribution to LVM of daily arterial blood pressure (BP) and insulin resistance in a consecutive series of 29 (mean+/-SD age, 43+/-13 yr) nonobese (body mass index, 24+/-1.8 kg/m2), nondiabetic, glucose-tolerant subjects with untreated borderline or mild hypertension [14]. Questionnable relevance to MLC.
• Characterization of the human IgG antibody VL repertoire to Haemophilus influenzae type b polysaccharide [15]. Wrong gene.
• When T cell lines and clones derived from lymphocytes infiltrating the ESRD kidneys were tested in MLKC, there was evidence of kidney-associated, as opposed to lymphocyte-associated (MLC) reactivity using (3H) thymidine uptake as a reflection of a lymphoproliferative response [16]. Relevance?
• CONCLUSIONS: Lisinopril decreases LVM in renal transplant patients with hypertension and LVH, and the ACE gene polymorphism may predict the beneficial effect of this therapy [17]. Relevance?

Biological context of MLC1

• We have investigated the relationship of MLC1 with SCZ and BPAD in Southern India. METHODS: All exons and flanking intronic sequences of MLC1 were screened for novel variations [5].
• Up-regulation expression of MLC1 in human liver cancer tissue and enhanced SMMC7721 cell tumorigenesis in vivo and vitro [1].
• RESULTS: RT-PCR results showed that 98.1% (245/250) was MLC1 up-regulation expression, 1.9% (5/250) was MLC1 down-regulation (p<0.01) [1].
• Members of the Agarwal ethnic group affected with the disorder present with a mildly progressive course and show a common mutation (320insC) in the MLC1 gene, suggesting a founder effect [18].
• METHODOLOGY: 250 cases of primary HCC tissue samples were studied for MLC1 mRNA and protein expression using RT-PCR, western blot, immunohistochemistry, MLC1 stable transfection into SMMC771, and SMMC7721 cells growth curve was analyzed by MTT method and SMMC7721 cells tumorigenesis in vivo [1].

Anatomical context of MLC1

• All patients underwent echocardiography (calculation of left ventricle ejection fraction--LVEF) and in the serum of all subjects NT-proBNP (ELEIA) and MLC-1 (ELISA) were determined [4]. Wrong gene?
• Myoblasts and myotubes synthesize the definitive light chains, MLC1 and MLC2 [19]. Wrong gene.
• MLC1 was detected in vivo and in heterologous systems at the plasma membrane [20].
• Other neuronal barriers, such as the ependyma and the pia mater, were also positive for MLC1 expression [20].
• MLC1 encodes a novel protein, MLC1, which is mainly expressed in the brain and leukocytes [21].

Associations of MLC1 with chemical compounds

• However, at doses below those needed for nuclear factor-kappaB inhibition, sulfasalazine was able to prevent TNF-alpha-induced barrier dysfunction, MLCK up-regulation, and MLC phosphorylation [22].
• Myoblasts were simultaneously identified using a MoAb directed against myosin light chains 1 and 2 (MLC1 and MLC2) and a combination of biotin-labelled sheep anti-mouse Ig antibody and Texas Red labelled streptavidin [23].
• A serum MLC1 level was elevated at presentation despite a normal creatine phosphokinase level [24].
• MLC1 levels more closely paralleled the clinical status than the aspartate aminotransferase and lactate dehydrogenase levels [24].
• In vitro studies showed that TNF caused similar increases in MLCK expression and MLC phosphorylation, as well as barrier dysfunction, in Caco-2 monolayers only after interferon (IFN)-gamma pretreatment [25].

Other interactions of MLC1

• Polymerase chain reaction (PCR) amplification of mRNA for human myoglobin and cardiac MLC1 confirmed the absence of their transcripts [26].
• Based on the dynamics of the Mlc1p-IQ protein-peptide complexes, the structure of the light-chain-binding domain of myosin V from the yeast S. cerevisiae is discussed [27].
• The Mlc1p protein from the budding yeast Saccharomyces cerevisiae is a Calmodulin-like protein, which interacts with IQ-motif peptides located at the yeast's myosin neck [27].
• Furthermore, our study revealed that pI shifts of the DIM-1 and MLC-1 proteins in the 2-DE gel were attributed to the presence of the acidic modifications [28].

Analytical, diagnostic and therapeutic context of MLC1

• Immunohistochemistry showed that 97.2% (243/250) was MLC1 up-regulation expression, 2.8% (7/250) was down-regulation (p<0.01) in cancer tissue compared with paracancerous tissue (p<0.01) [1].
• Western blotting results showed that 98.9% (247/250) was MLC1 up-regulation expression, 1.1% (3/250) was MLC1 down-regulation [1].
• An Adult Case of Megalencephalic Leukoencephalopathy with Subcortical Cysts with S93L Mutation in MLC1 Gene: A Case Report and Diffusion MRI [29].
• The results suggest that MLC1 levels may facilitate the early diagnosis and management of patients with inflammatory myopathy [24]. Wrong gene.
• Results: Colitis induced in vivo by adoptive transfer of CD4(+)CD45RB(hi) T cells was associated with increased epithelial MLCK expression and myosin II regulatory light chain (MLC) phosphorylation as well as morphologic tight junction disruption [25]. Wrong gene.

References