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Qiuyue Chen, Bray Denard, Ching-En Lee, Sungwon Han, James S Ye, Jin Ye
TM4SF20 (transmembrane 4 L6 family 20) is a polytopic membrane protein that inhibits proteolytic processing of CREB3L1 (cAMP response element-binding protein 3-like 1), a membrane-bound transcription factor that blocks cell division and activates collagen synthesis. Here we report that ceramide stimulates CREB3L1 cleavage by inverting the orientation of TM4SF20 in membranes. In the absence of ceramide, the N terminus of the first transmembrane helix of TM4SF20 is inserted into the endoplasmic reticulum (ER) lumen...
August 18, 2016: Molecular Cell
Qiuyue Chen, Ching-En Lee, Bray Denard, Jin Ye
CREB3L1 (cAMP response element binding protein 3-like 1), a transcription factor synthesized as a membrane-bound precursor and activated through Regulated Intramembrane Proteolysis (RIP), is essential for collagen production by osteoblasts during bone development. Here, we show that TGF-β (transforming growth factor-β), a cytokine known to stimulate production of collagen during wound healing and fibrotic diseases, induces proteolytic activation of CREB3L1 in human A549 cells. This activation results from inhibition of expression of TM4SF20 (transmembrane 4 L6 family member 20), which normally inhibits RIP of CREB3L1...
2014: PloS One
Wojciech Wiszniewski, Jill V Hunter, Neil A Hanchard, Jason R Willer, Chad Shaw, Qi Tian, Anna Illner, Xueqing Wang, Sau W Cheung, Ankita Patel, Ian M Campbell, Violet Gelowani, Patricia Hixson, Audrey R Ester, Mahshid S Azamian, Lorraine Potocki, Gladys Zapata, Patricia P Hernandez, Melissa B Ramocki, Regie L P Santos-Cortez, Gao Wang, Michele K York, Monica J Justice, Zili D Chu, Patricia I Bader, Lisa Omo-Griffith, Nirupama S Madduri, Gunter Scharer, Heather P Crawford, Pattamawadee Yanatatsaneejit, Anna Eifert, Jeffery Kerr, Carlos A Bacino, Adiaha I A Franklin, Robin P Goin-Kochel, Gayle Simpson, Ladonna Immken, Muhammad E Haque, Marija Stosic, Misti D Williams, Thomas M Morgan, Sumit Pruthi, Reed Omary, Simeon A Boyadjiev, Kay K Win, Aye Thida, Matthew Hurles, Martin Lloyd Hibberd, Chiea Chuen Khor, Nguyen Van Vinh Chau, Thomas E Gallagher, Apiwat Mutirangura, Pawel Stankiewicz, Arthur L Beaudet, Mirjana Maletic-Savatic, Jill A Rosenfeld, Lisa G Shaffer, Erica E Davis, John W Belmont, Sarah Dunstan, Cameron P Simmons, Penelope E Bonnen, Suzanne M Leal, Nicholas Katsanis, James R Lupski, Seema R Lalani
White matter hyperintensities (WMHs) of the brain are important markers of aging and small-vessel disease. WMHs are rare in healthy children and, when observed, often occur with comorbid neuroinflammatory or vasculitic processes. Here, we describe a complex 4 kb deletion in 2q36.3 that segregates with early childhood communication disorders and WMH in 15 unrelated families predominantly from Southeast Asia. The premature brain aging phenotype with punctate and multifocal WMHs was observed in ~70% of young carrier parents who underwent brain MRI...
August 8, 2013: American Journal of Human Genetics
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