The male abnormal gene family 21 (), was initially identified in . Since its identification, studies from different groups have shown that it regulates development of ocular tissues, brain, heart and liver. However, its functional mechanism remains largely unknown. Here, we demonstrate that Mab21L1 promotes survival of lens epithelial cells. Mechanistically, Mab21L1 upregulates expression of αB-crystallin. Moreover, our results show that αB-crystallin prevents stress-induced phosphorylation of p53 at S-20 and S-37 through abrogating the activation of the upstream kinases, ATR and CHK1. As a result of suppressing p53 activity by αB-crystallin, Mab21L1 downregulates expression of Bak but upregulates Mcl-1 during stress insult. Taken together, our results demonstrate that Mab21L1 promotes survival of lens epithelial cells through upregulation of αB-crystallin to suppress ATR/CHK1/p53 pathway.
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http://dx.doi.org/10.18632/aging.204203 | DOI Listing |
Anat Rec (Hoboken)
May 2024
Department of Veterinary Anatomy, The University of Tokyo, Tokyo, Japan.
The cerebellar, ocular, craniofacial, and genital (COFG) syndrome is a human genetic disease that is caused by MAB21L1 mutations. A COFG mouse model with Mab21l1-null mutation causes severe microphthalmia and fontanelle dysosteogenesis, similar to the symptoms in human patients. One of the typical symptoms is scrotal agenesis in male infants, while male Mab21l1-null mice show hypoplastic preputial glands, a rodent-specific derivative of the cranial scrotal fold.
View Article and Find Full Text PDFAging (Albany NY)
August 2022
College of Life Sciences, Hunan Normal University, Changsha 410080, Hunan, China.
The male abnormal gene family 21 (), was initially identified in . Since its identification, studies from different groups have shown that it regulates development of ocular tissues, brain, heart and liver. However, its functional mechanism remains largely unknown.
View Article and Find Full Text PDFPLoS One
February 2007
Biology Department, Pennsylvania State University, University Park, Pennsylvania, United States of America.
Developmental proteins play a pivotal role in the origin of animal complexity and diversity. We report here the identification of a highly divergent developmental protein superfamily (DANGER), which originated before the emergence of animals (approximately 850 million years ago) and experienced major expansion-contraction events during metazoan evolution. Sequence analysis demonstrates that DANGER proteins diverged via multiple mechanisms, including amino acid substitution, intron gain and/or loss, and recombination.
View Article and Find Full Text PDFJ Cell Physiol
April 2007
Department of Biochemistry and BK 21 Program, Kyungpook National University, Daegu, Korea.
Myeloid Elf-1 like factor (MEF) is a member of the Ets transcription factor family. Ets family proteins control the expression of genes that are critical for biological processes such as proliferation, differentiation, and cell death. Some of Ets factors are also known to regulate bone development.
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