Wenyu Yu

Beclin 1-independent autophagy induced by a Bcl-XL/Bcl-2 targeting compound, Z18.

Inhibitors of Bcl-XL/Bcl-2 can induce autophagy by releasing the autophagic protein Beclin 1 from its complexes with these proteins. Here we report a novel compound targeting the BH3 binding groove of Bcl-XL/Bcl-2, Z18, which efficiently induces autophagy-associated cell death in HeLa cells, without apparent apoptosis. Unexpectedly, the inhibition of Beclin 1 and phosphatidylinositol 3-kinase have no obvious effect on Z18-induced autophagy in HeLa cells, implying that it is a non-canonical Beclin 1-independent autophagy. Meanwhile, the accumulation of autophagosomes is positively correlated with Z18-induced cell death and the full flux of autophagy is not necessary.

A novel Bcl-XL inhibitor Z36 that induces autophagic cell death in Hela cells

Inhibition of Bcl2 family proteins Bcl-XL and Bcl-2 represents a promising drug development strategy for cancer treatment by triggering apoptosis in cancer cells. Here we report a novel Bcl-XL inhibitor, Z36, which unexpectedly induces only autophagic cell death, but not apoptosis. This special property distinguishes Z36 from other previously reported Bcl-XL and Bcl-2 inhibitors that induce cancer cell death mainly through apoptosis, and makes Z36 an attractive molecular tool for studying the cellular regulation of autophagic cell death and apoptosis.

Structural and functional characterization of tumor suppressors TIG3 and H-REV107

H‐REV107‐like family proteins TIG3 and H‐REV107 are class II tumor suppressors. Here we report that the C‐terminal domains (CTDs) of TIG3 and H‐REV107 can induce HeLa cell death independently. The N‐terminal domain (NTD) of TIG3 enhances the cell death inducing ability of CTD, while NTD of H‐REV107 plays an inhibitory role. The solution structure of TIG3 NTD is very similar to that of H‐REV107 in overall fold. However, the CTD binding regions on NTD are different between TIG3 and H‐REV107, which may explain their functional difference. As a result, the flexible main loop of H‐REV107, but not that of TIG3, is critical for its NTD to modulate its CTD in inducing cell death.

1H, 13C, and 15N resonance assignments of a general stress protein GSP13 from Bacillus subtilis

GSP13 encoded by gene yugI is a general stress protein in Bacillus subtilis. The NMR assignments of the protein are essential for its structure determination.

Solution structure of GSP13 from Bacillus subtilis exhibits an S1 domain related to cold shock proteins

GSP13 encoded by gene yugI is a σB-dependent general stress protein in Bacillus subtilis, which can be induced by heat shock, salt stress, ethanol stress, glucose starvation, oxidative stress and cold shock. Here we report the solution structure of GSP13 and it is the first structure of S1 domain containing protein in Bacillus subtilis. The structure of GSP13 mainly consists of a typical S1 domain along with a C-terminal 50-residue flexible tail, different from the other known S1 domain containing proteins. Comparison with other S1 domain structures reveals that GSP13 has a conserved RNA binding surface, and it may function similarly to cold shock proteins in response to cold stress.

1H, 13C, and 15N resonance assignments of human ζ-COP

The ζ-COP is one subunit of the COP I coatomer, which mediates the protein trafficking from the cis-Golgi complex to the endoplasmic reticulum and also functions in the intra-Golgi trafficking. The NMR assignments of the ζ-COP are essential for its solution structure determination.