SPOP point mutations regulate substrate preference and affect its function.

The adaptor SPOP recruits substrates to CUL3 E3 ligase for ubiquitination and degradation. Structurally, SPOP harbors a MATH domain for substrate recognition, and a BTB domain responsible for binding CUL3. Reported point mutations always occur in SPOP's MATH domain and are through to disrupt affinities of SPOP to substrates, thereby leading to tumorigenesis. In this study, we identify the tumor suppressor IRF2BP2 as a novel substrate of SPOP. SPOP enables to attenuate IRF2BP2-inhibited cell proliferation and metastasis in HCC cells. However, overexpression of wild-type SPOP alone suppresses HCC cell proliferation and metastasis. In addition, a HCC-derived mutant, SPOP-M35L, shows an increased affinity to IRF2BP2 in comparison with wild-type SPOP. SPOP-M35L promotes HCC cell proliferation and metastasis, suggesting that M35L mutation possibly reprograms SPOP from a tumor suppressor to an oncoprotein. Taken together, this study uncovers mutations in SPOP's MATH lead to distinct functional consequences in context-dependent manners, rather than simply disrupting its interactions with substrates, raising a noteworthy concern that we should be prudent to select SPOP as therapeutic target for cancers.

Shear Behavior of Hybrid Fiber Reinforced Concrete Deep Beams.

Hybrid fiber reinforced concrete (HFRC) is based on a multilevel-reinforcement material design that improves both the compressive strength and tensile strength. Investigations of the mechanical performance of HFRC with two types of steel fibers were conducted experimentally. The investigated parameters were the volume fractions of the short steel fibers and long steel fibers. The compressive strength, tensile strength, and flexural strength of the HFRC were researched. The group with volume fractions of 1.5% for the long steel fibers and 0.5% for the short steel fibers exhibited the best flexural strength. The synergetic effect clearly was improved by combining different types of steel fiber. Four HFRC deep beams and one reinforced concrete (RC) deep beam were conducted to consider the shear behavior of these beams. The primary variables included the volume fraction of steel fibers and the web reinforcement ratio. The shear behavior was evaluated based on the cracking pattern, load-deflection behavior, and shear capacity. All of the beams failed due to the formation of diagonal cracks. The results indicated that hybrid fibers contribute greatly to the shear behavior of deep beams. The hybrid fibers led to the formation of multiple diagonal cracks in the deep beams and enhanced the damage tolerance. With the same web reinforcement ratio, the ultimate load and deformation of the HFRC deep beams were better than those of the RC deep beam.