Min-Sik Lee

The activity of the phosphatase and tensin homologue (PTEN) is known to be suppressed via post-translational modification. However, the mechanism and physiological significance by which post-translational modifications lead to PTEN suppression remain unclear. Here we demonstrate that PTEN destabilization is induced by EGFR- or oncogenic PI3K mutation-mediated AKT activation in cervical cancer. EGFR/PI3K/AKT-mediated ubiquitination and degradation of PTEN are dependent on the MKRN1 E3 ligase. The

BACKGROUND: We investigated whether Makorin ring finger protein 1 (MKRN1), an E3 ligase, affects p14ARF-associated cellular senescence and tumorigenesis by posttranslational modification in gastric tumorigenesis. METHODS: A link between MKRN1 and ARF was examined in MKRN1 null mouse embryonic fibroblasts (MEFs) and in human fibroblasts and gastric cancer cells by silencing MKRN1 using small interfering RNA (siRNA) and short hairpin RNA (shRNA). Ubiquitination and proteasomal degradation assays w

AMP-activated protein kinase (AMPK) plays a key role in controlling energy metabolism in response to physiological and nutritional status. Although AMPK activation has been proposed as a promising molecular target for treating obesity and its related comorbidities, the use of pharmacological AMPK activators has been met with contradictory therapeutic challenges. Here we show a regulatory mechanism for AMPK through its ubiquitination and degradation by the E3 ubiquitin ligase makorin ring finger

Pancreatic ductal adenocarcinoma (PDA) is a lethal, therapy-resistant cancer that thrives in a highly desmoplastic, nutrient-deprived microenvironment. Several studies investigated the effects of depriving PDA of either glucose or glutamine alone. However, the consequences on PDA growth and metabolism of limiting both preferred nutrients have remained largely unknown. Here, we report the selection for clonal human PDA cells that survive and adapt to limiting levels of both glucose and glutamine.

The tumor suppressor function of p14ARF is regulated at a posttranslational level via mechanisms yet to be fully understood. Here, we report the identification of an unconventional p14ARF degradation pathway induced by the chaperone HSP90 in association with the E3 ubiquitin ligase C-terminus of HSP70-interacting protein (CHIP). The ternary complex of HSP90, CHIP, and p14ARF was required to induce the lysosomal degradation of p14ARF by an ubiquitination-independent but LAMP2A-dependent mechanism

Significance To date, therapies are lacking that efficiently target the Kirsten rat sarcoma ( KRAS ) oncogene, which is responsible for approximately a quarter of all lung cancer cases in the United States. This study provides genetic evidence that the insulin/insulin-like growth factor 1 (IGF1) signaling, which modulates cellular survival, growth, and metabolism, is required for KRAS -driven lung cancer initiation. It further identifies a metabolic vulnerability in tumors with loss of such sign

PPARγ (Peroxisome proliferator-activated receptor γ) is a nuclear receptor involved in lipid homeostasis and related metabolic diseases. Acting as a transcription factor, PPARγ is a master regulator for adipocyte differentiation. Here, we reveal that CHIP (C-terminus of HSC70-interacting protein) suppresses adipocyte differentiation by functioning as an E3 ligase of PPARγ. CHIP directly binds to and induces ubiquitylation of the PPARγ protein, leading to proteasome-dependent degradation. Stable

The tumor suppressor p53, long known for its roles in maintaining genomic integrity and suppressing tumorigenesis, has recently been recognized as a key regulator of cellular metabolism. Here, we review p53's emerging metabolic functions, highlighting its ability to orchestrate glucose, amino acid, and lipid metabolism. By promoting oxidative phosphorylation while inhibiting glycolysis and anabolic pathways, wild-type p53 counters metabolic reprogramming characteristic of cancer cells, such as t

Abstract The activity of the phosphatase and tensin homologue (PTEN) is known to be suppressed via post-translational modification. However, the mechanism and physiological significance by which post-translational modifications lead to PTEN suppression remain unclear. Here we demonstrate that PTEN destabilization is induced by EGFR- or oncogenic PI3K mutation-mediated AKT activation in cervical cancer. EGFR/PI3K/AKT-mediated ubiquitination and degradation of PTEN are dependent on the MKRN1 E3 li

The most popular reconstruction algorithm for cone-beam computed tomography (CBCT) is based on the computationally-inexpensive filtered-backprojection (FBP) method. However, that method usually requires dense projections over the Nyquist samplings, which imposes severe restrictions on the imaging doses. Moreover, the algorithm tends to produce cone-beam artifacts as the cone angle is increased. Several variants of the FBP-based algorithm have been developed to overcome these difficulties, but pr

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20178-0.