Opposing roles of HDAC6 in liver regeneration and hepatocarcinogenesis.

Histone deacetylase 6 (HDAC6), a deacetylase of p53, has emerged as a privileged inhibitory target for cancer therapy because of its deacetylating activity for p53 at K120 and K373/382. However, intricate roles of HDAC6 in hepatocellular carcinogenesis have been suggested by recent evidence, namely that HDAC6 ablation suppresses innate immunity, which plays critical roles in tumor immunosurveillance and antitumor immune responses. Therefore, it is valuable to determine whether HDAC6 ablation inhibits hepatocellular carcinogenesis using in vivo animal models.

p32/C1QBP regulates OMA1-dependent proteolytic processing of OPA1 to maintain mitochondrial connectivity related to mitochondrial dysfunction and apoptosis.

Mitochondria are dynamic organelles that undergo fusion and fission in response to various physiological and stress stimuli, which play key roles in diverse mitochondrial functions such as energy metabolism, intracellular signaling, and apoptosis. OPA1, a mitochondrial dynamin-like GTPase, is responsible for the inner membrane fusion of mitochondria, and the function of OPA1 is regulated by proteolytic cleavage in response to various metabolic stresses. Growing evidences highlighted the importance of mitochondrial adaptation in response to metabolic stimuli.

HDAC6 regulates thermogenesis of brown adipocytes through activating PKA to induce UCP1 expression.

Mitochondrial uncoupling protein 1 (UCP1) is responsible for nonshivering thermogenesis in brown adipose tissue (BAT). UCP1 increases the conductance of the inner mitochondrial membrane (IMM) for protons to make BAT mitochondria generate heat rather than ATP. HDAC6 is a cytosolic deacetylase for non-histone substrates to regulate various cellular processes, including mitochondrial quality control and dynamics.

HDAC6 deficiency induces apoptosis in mesenchymal stem cells through p53 K120 acetylation.

The acetylation of p53 is critical in modulating its pro-apoptotic roles. However, its regulatory mechanism and physiological significance are unclear. Here, we show HDAC6 negatively regulates pro-apoptotic acetylation of p53 at lysine residue 120 (K120) in mesenchymal stem cells (MSCs).

RAP80 binds p32 to preserve the functional integrity of mitochondria.

RAP80, a member of the BRCA1-A complex, is a well-known crucial regulator of cell cycle checkpoint and DNA damage repair in the nucleus. However, it is still unclear whether Rap80 localizes to another region outside the nucleus and plays different roles with its partners. Here, we found mitochondrial p32 as a novel binding partner of RAP80 by using yeast two-hybrid screening.

A synthetic isoflavone, DCMF, promotes human keratinocyte migration by activating Src/FAK signaling pathway.

Flavonoids are plant secondary compounds with various pharmacological properties. We previously showed that one flavonoid, trimethoxyisoflavone (TMF), could promote wound healing by inducing keratinocyte migration. Here, we screened TMF derivatives for enhanced activity and identified one compound, 2',6 Dichloro-7-methoxyisoflavone (DCMF), as most effective at promoting migration in a scratch wound assay.