• Emerging role of transient receptor potential (TRP) channels in cancer progression

    A schematic diagram comparing the protein structures of TRP subfamilies. TRP proteins carry six transmembrane segments (S1 to S6). (A, E) TRPC and TRPP subfamilies contain EF hand domain that binds intracellular Ca2+. (A) CIRB is a calmodulin/IP3R-binding domain. (B, E) TRPML and TRPP contain ER retention signlaling domain. (C) NUDIX, named after nucleoside diphosphate-linked moiety-X, is a homologous region in the phosphohydrolase family that binds to ADP ribose. The NUDIX represents a unique activation mechanism, gating by ADP ribose, on TRPM2. Other activators, such as cyclic ADPR and NAD+, as well as inhibitors also target the NUDIX. C-terminal serine/threonine kinase is similar in structure to protein kinase A. (D) TRPV contains ARD and TRP box, similar to TRPC. (F) TRPA1 contains more than 14 ARDs at its N-terminus.
  • Mechanistic insights into differential requirement of receptor dimerization for oncogenic activation of mutant EGFR and its clinical perspective

    Proposed model of dimerization requirements for receptor activation by wildtype EGFR and oncogenic mutants (adapted from Cho et al., 2013). (A) Activation of wildtype EGFR is initiated by ligand-induced extracellular dimerization of the receptor, which in turn direct “outside-in” asymmetric dimerization of the N- and C-lobes in the kinase domain, leading to enzymatic activation of the receiver monomer and subsequent autophosphorylation on the C-terminal tail of the activator monomer. Therefore, full enzymatic activation and consequent signaling cascade of the wildtype EGFR are tightly dependent on all sequential events of ligand binding, dimerization and autophosphorylation. (B) A group of EGFR mutants including the L858R, most colon cancer-derived and C-terminal truncation EGFR mutants are able to form constitutive asymmetric dimerization irrespective of ligand binding, which in turn promotes “inside-out” extracellular dimerization; ligand increases dimerization but is not required. Interruption of dimerization impairs the oncogenic activity of these types of mutant EGFR because the receiver monomer is no longer active. Thus, mutant EGFR belong to this group is sensitive to EGFR-directed mAs such as cetuximab. (C) In contrast, a subset of mutant EGFR including the Ex19Del and Ex20Ins mutants and the L858R/T790M double mutants similarly undergo dimerization in the absence of ligand, but do not require dimerization for their activity. These mutant forms of EGFR acquire the oncogenic activity in dimerization-independent manner so that these mutants are refractory to EGFR mAbs.

BMB Reports 2020; 53(3): 125~171
Invited Mini Reviews
Emerging role of transient receptor potential (TRP) channels in cancer progression
Dongki Yang & Jaehong Kim
BMB Reports 2020; 53(3): 125-132  https://doi.org/10.5483/BMBRep.2020.53.3.016
Mechanistic insights into differential requirement of receptor dimerization for oncogenic activation of mutant EGFR and its clinical perspective
Jeonghee Cho
BMB Reports 2020; 53(3): 133-141  https://doi.org/10.5483/BMBRep.2020.53.3.025
Articles
Sinapic acid induces the expression of thermogenic signature genes and lipolysis through activation of PKA/CREB signaling in brown adipocytes
Monir Hossain, Khan Mohammad Imran, Md. Shamim Rahman, Dahyeon Yoon, Vignesh Marimuthu & Yong-Sik Kim
BMB Reports 2020; 53(3): 142-147  https://doi.org/10.5483/BMBRep.2020.53.3.093
Co-administration of erythropoietin and iron complex improves late-phase liver regeneration
Ji-Yoon Kim, Dongho Choi, Joohwan Kim, Young-Myeong Kim, Hyunyoung Lim, Jeong Min Sung, Min Kyu Lee, Yoo Jin Choung, Ji Hee Chang & Mi Ae Jeong
BMB Reports 2020; 53(3): 148-153  https://doi.org/10.5483/BMBRep.2020.53.3.160
Physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via regulating calcium signaling
Ning Ding, Yanzhu Lu, Hanmin Cui, Qinyu Ma, Dongxia Qiu, Xueting Wei, Ce Dou & Ning Cao
BMB Reports 2020; 53(3): 154-159  https://doi.org/10.5483/BMBRep.2020.53.3.147
Overexpression of three related root-cap outermost-cell-specific C2H2-type zinc-finger protein genes suppresses the growth of Arabidopsis in an EAR-motif-dependent manner
Sang-Kee Song, Hyeon-Ung Jang, Yo Han Kim, Bang Heon Lee & Myeong Min Lee
BMB Reports 2020; 53(3): 160-165  https://doi.org/10.5483/BMBRep.2020.53.3.286
Antiviral activity of sertindole, raloxifene and ibutamoren against transcription and replication-competent Ebola virus-like particles
Yi-Seul Yoon, Yejin Jang, Thomas Hoenen, Heegwon Shin, Younghoon Lee & Meehyein Kim
BMB Reports 2020; 53(3): 166-171  https://doi.org/10.5483/BMBRep.2020.53.3.175

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March 2020
Volume 53
Issue 3

2018 SCI Impact Factor 2.966

BIOCHEMISTRY & MOLECULAR BIOLOGY 134/292

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