Embryonic growth-associated protein is one subunit of a novel N-terminal acetyltransferase complex essential for embryonic vascular development.
Embryonic growth-associated protein is one subunit of a novel N-terminal acetyltransferase complex essential for embryonic vascular development.
复制标题
胚胎生长相关蛋白是胚胎血管发育所必需的新型 N 末端乙酰转移酶复合物的一个亚基。
DOI：
10.1161/01.res.0000214539.86593.7a
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Weiser-Evans,MaryCM
中科院分区：
文献类型：
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作者：
Wenzlau,JanetM;Garl,PamelaJ;Simpson,Peter;Stenmark,KurtR;West,James;Artinger,KristinB;Nemenoff,RaphaelA;Weiser-Evans,MaryCM
N-terminal protein acetylation, catalyzed by N-terminal acetyltransferases (NATs) recognizing distinct N-terminal sequences, is gaining recognition as an essential regulator of normal cell function, but little is known of its role in vertebrate development. We previously cloned a novel gene, embryonic growth-associated protein (EGAP), the expression of which is associated with rapid vascular smooth muscle cell proliferation during development. We show herein EGAP is the mammalian/zebrafishhomologue of yeast Mak10p, one subunit of the yeast NatC complex, and describe the cloning of its binding partners Mak3 and Mak31. The EGAP NAT forms a functional complex in mammalian cells, is evolutionarily conserved, and developmentally regulated. It is widely but not ubiquitously expressed during earlyzebrafishdevelopment but undetectable in later developmental stages. We demonstrate EGAP- and Mak3-deficientzebrafishfail to develop because of, in part, decreased cell proliferation, increased apoptosis, and poor blood vessel formation contributing to embryonic lethality. We examined the role of target of rapamycin (TOR), a highly conserved protein kinase controlling cell growth, as a physiological target of EGAP NAT acetylation. Compared with controls, TOR expression and signaling is significantly reduced in EGAP morphants. Pharmacological inhibition of TOR with rapamycin phenocopied the EGAP morpholino oligonucleotide-induced growth and vessel defects. Overexpression of constitutively active TOR rescued EGAP morphants, suggesting TOR is a direct or indirect endogenous substrate of the EGAP NAT complex. These data suggest the EGAP NAT complex is an essential regulatory enzyme controlling the function of a subset of proteins required for embryonic growth control and vessel development.
