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Journal Mol Cell Biol

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Genome-wide regulations of the pre-initiation complex formation and elongating RNA polymerase II by an E3 ubiquitin ligase, San1.

Priyanka Barman, Rwik Sen, Amala Kaja, Jannatul Ferdoush, Shalini Guha, Chhabi K Govind, Sukesh R Bhaumik,

San1 ubiquitin ligase is involved in nuclear protein quality control via its interaction with intrinsically disordered proteins for ubiquitylation and proteasomal degradation. Since several transcription/chromatin regulatory factors contain intrinsically disordered domains and can be inhibitory to transcription when in excess, San1 might be involved in transcription regulation. To address this, ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, :MCB0036821]

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DNA damage-induced phosphorylation of histone H2A at serine 15 is linked to DNA end resection.

Salar Ahmad, Valérie Côté, Jacques Côté,

The repair of DNA double-strand breaks (DSBs) occurs in chromatin and several histone post-translational modifications have been implicated in the process. Modifications of histone H2A N-terminal tail has also been linked to DNA damage response, through acetylation or ubiquitination of lysine residues that regulate repair pathway choice. Here, we characterize ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, :MCB0005621]

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SUMO Modification of PAF1/PD2 Enables PML Interaction and Promotes Radiation Resistance in Pancreatic Ductal Adenocarcinoma.

Sanchita Rauth, Saswati Karmakar, Ashu Shah, Parthasarathy Seshacharyulu, Rama Krishna Nimmakayala, Koelina Ganguly, Rakesh Bhatia, Sakthivel Muniyan, Sushil Kumar, Samikshan Dutta, Chi Lin, Kaustubh Datta, Surinder K Batra, Moorthy P Ponnusamy,

RNA polymerase II-associated factor 1 (PAF1)/pancreatic differentiation 2 (PD2) is a core subunit of the human PAF1 complex (PAF1C) that regulates the RNA polymerase II function during transcriptional elongation. PAF1/PD2 has also been linked to the oncogenesis of pancreatic ductal adenocarcinoma (PDAC). Here, we report that PAF1/PD2 undergoes post-translational modification ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, :MCB0013521]

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The ASCIZ-DYNLL1 axis is essential for TLR4-mediated antibody responses and NF-κB pathway activation.

Rui Liu, Ashleigh King, David Tarlinton, Jörg Heierhorst,

Toll-like receptors (TLRs) and IL-1 receptors regulate immune and inflammatory responses by activating the nuclear factor (NF)-κB pathway. Here we report that B cell-specific loss of Dynein light chain-1 (DYNLL1, LC8) or its designated transcription factor ASCIZ (ATMIN) leads to severely reduced <i>in vivo</i> antibody responses to TLR4-dependent but not ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, :MCB0025121]

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Viral manipulation of a mechanoresponsive signaling axis disassembles processing bodies.

Elizabeth L Castle, Carolyn-Ann Robinson, Pauline Douglas, Kristina D Rinker, Jennifer A Corcoran,

Processing bodies (PBs) are ribonucleoprotein granules important for cytokine mRNA decay that are targeted for disassembly by many viruses. Kaposi's sarcoma-associated herpesvirus is the etiological agent of the inflammatory endothelial cancer, Kaposi's sarcoma, and a PB-regulating virus. The virus encodes Kaposin B (KapB), which induces actin stress fibres (SFs) and ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, :MCB0039921]

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Mnt represses epithelial identity to promote Epithelial to Mesenchymal Transition.

Deborah P Lavin, Leila Abassi, Mohammed Inayatullah, Vijay K Tiwari,

The multi-step process of epithelial to mesenchymal transition (EMT), whereby static epithelial cells become migratory mesenchymal cells, plays a critical role during various developmental contexts, wound healing, and pathological conditions such as cancer metastasis. Despite the established function of basic helix-loop-helix (bHLH) transcription factors (TFs) in cell-fate determination, only a ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, :MCB0018321]

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Regulation of estradiol synthesis by aromatase interacting partner (AIPB).

Himangshu S Bose, Randy M Whittal, Curtis E Lanier, Brendan Marshall, Maheshinie Rajapaksha, Brian W Wheeler, Nicholas D Carbo, Elin M Hahn, Elizabeth W Perry, Neal M Hall, Mikhail M Melomed, Edward L Perkins, William E Burak,

Estradiol is essential for the development of female sex characteristics and fertility. Postmenopausal women and breast cancer patients have high estradiol. Aromatase catalyzes estradiol synthesis; however, the factors regulating aromatase activity are unknown. We identified a new 22-kDa protein, aromatase interacting partner in breast (AIPB), from the endoplasmic reticulum of ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, :MCB0035721]

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Rewiring of Lactate-Interleukin-1β Autoregulatory Loop with Clock-Bmal1: a Feed-Forward Circuit in Glioma.

Pruthvi Gowda, Kirti Lathoria, Shalini Sharma, Shruti Patrick, Sonia B Umdor, Ellora Sen,

A desynchronized circadian rhythm in tumors is coincident with aberrant inflammation and dysregulated metabolism. As their interrelationship in cancer etiology is largely unknown, we investigated the link among the three in glioma. The tumor metabolite lactate-mediated increase in the proinflammatory cytokine interleukin-1β (IL-1β) was concomitant with elevated levels of the ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(9):e0044920]

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Correction for Burton et al., "Targeting the Nuclear Cathepsin L CCAAT Displacement Protein/Cut Homeobox Transcription Factor-Epithelial Mesenchymal Transition Pathway in Prostate and Breast Cancer Cells with the Z-FY-CHO Inhibitor".

Liza J Burton, Jodi Dougan, Jasmine Jones, Bethany N Smith, Diandra Randle, Veronica Henderson, Valerie A Odero-Marah,

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(9):e0025621]

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FANCD2-Associated Nuclease 1 Partially Compensates for the Lack of Exonuclease 1 in Mismatch Repair.

Katja Kratz, Mariela Artola-Borán, Saho Kobayashi-Era, Gene Koh, Goncalo Oliveira, Shunsuke Kobayashi, Andreia Oliveira, Xueqing Zou, Julia Richter, Masataka Tsuda, Hiroyuki Sasanuma, Shunichi Takeda, Joanna I Loizou, Alessandro A Sartori, Serena Nik-Zainal, Josef Jiricny,

Germline mutations in the mismatch repair (MMR) genes <i>MSH2</i>, <i>MSH6</i>, <i>MLH1</i>, and <i>PMS2</i> are linked to cancer of the colon and other organs, characterized by microsatellite instability and a large increase in mutation frequency. Unexpectedly, mutations in <i>EXO1</i>, encoding the only exonuclease genetically implicated in MMR, are not linked to ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(9):e0030321]

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RNA-Binding Proteins PCBP1 and PCBP2 Are Critical Determinants of Murine Erythropoiesis.

Xinjun Ji, Anupama Jha, Jesse Humenik, Louis R Ghanem, Andrew Kromer, Christopher Duncan-Lewis, Elizabeth Traxler, Mitchell J Weiss, Yoseph Barash, Stephen A Liebhaber,

We previously demonstrated that the two paralogous RNA-binding proteins PCBP1 and PCBP2 are individually essential for mouse development: <i>Pcbp1</i>-null embryos are peri-implantation lethal, while <i>Pcbp2</i>-null embryos lose viability at midgestation. Midgestation <i>Pcbp2</i><sup>-/-</sup> embryos revealed a complex phenotype that included loss of certain hematopoietic determinants. Whether PCBP2 directly contributes to erythropoietic ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(9):e0066820]

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The Cyclin-Dependent Kinase 8 (CDK8) Inhibitor DCA Promotes a Tolerogenic Chemical Immunophenotype in CD4+ T Cells via a Novel CDK8-GATA3-FOXP3 Pathway.

Azlann Arnett, Keagan G Moo, Kaitlin J Flynn, Thomas B Sundberg, Liv Johannessen, Alykhan F Shamji, Nathanael S Gray, Thomas Decker, Ye Zheng, Vivian H Gersuk, Ziaur S Rahman, David E Levy, Isabelle J Marié, Peter S Linsley, Ramnik J Xavier, Bernard Khor,

Immune health requires innate and adaptive immune cells to engage precisely balanced pro- and anti-inflammatory forces. We employ the concept of chemical immunophenotypes to classify small molecules functionally or mechanistically according to their patterns of effects on primary innate and adaptive immune cells. The high-specificity, low-toxicity cyclin-dependent kinase 8 (CDK8) ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(9):e0008521]

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Huntingtin Polyglutamine Fragments Are a Substrate for Hsp104 in Yeast.

Nicole J Wayne, Katherine E Dembny, Tyler Pease, Farrin Saba, Xiaohong Zhao, Daniel C Masison, Lois E Greene,

The aggregation of huntingtin fragments with expanded polyglutamine repeat regions (HttpolyQ) that cause Huntington's disease depends on the presence of a prion with an amyloid conformation in yeast. As a result of this relationship, HttpolyQ aggregation indirectly depends on Hsp104 due to its essential role in prion propagation. We find ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, :MCB0012221]

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Inhibition of Long Noncoding RNA SNHG20 Improves Angiotensin II-Induced Cardiac Fibrosis and Hypertrophy by Regulating the MicroRNA 335/Galectin-3 Axis.

Mingyang Li, Chunli Qi, Renxing Song, Chunming Xiong, Xiao Zhong, Ziguang Song, Zhongping Ning, Xiang Song,

Cardiac fibrosis is a hallmark of various heart diseases and ultimately leads to heart failure. Although long noncoding RNA (lncRNA) <i>SNHG20</i> has been reported to play important roles in various cancers, its function in cardiac fibrosis remains unclear. The expression of <i>SNHG20</i> and microRNA 335 (miR-335) in heart tissues of ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(9):e0058020]

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A catalytic-independent function of human DNA polymerase Kappa controls the stability and abundance of the Checkpoint Kinase 1.

Marina Dall'Osto, Laura Pierini, Nicolas Valery, Jean-Sébastien Hoffmann, Marie-Jeanne Pillaire,

DNA polymerase kappa (Pol κ) has been well documented thus far for its specialized DNA synthesis activity during translesion replication, progression of replication forks through regions difficult to replicate, restart of stalled forks and replication checkpoint efficiency. Pol κ is also required for the stabilization of stalled forks although the ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, :MCB0009021]

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IRC3 regulates mitochondrial translation in response to metabolic cues in Saccharomyces cerevisiae.

Jaswinder Kaur, Kaustuv Datta,

Mitochondrial oxidative phosphorylation (OXPHOS) enzymes are made up of dual genetic origin. Mechanisms regulating the expression of nuclear-encoded OXPHOS subunits in response to metabolic cues (glucose vs. glycerol), is significantly understood while regulation of mitochondrially encoded OXPHOS subunits is poorly defined. Here, we show that <i>IRC3</i> a DEAD/H box helicase, ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, :MCB0023321]

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Circular RNA circ-ERBB2 Elevates the Warburg Effect and Facilitates Triple-Negative Breast Cancer Growth by the MicroRNA 136-5p/Pyruvate Dehydrogenase Kinase 4 Axis.

Yihong Huang, Shuo Zheng, Ying Lin, Liming Ke,

Triple-negative breast cancer (TNBC) is an aggressive histological subtype of breast cancer. It has been reported that the circular RNA (circRNA) circ-ERBB2 (circBase identifier hsa_circ_0007766) is mainly distributed in the cytoplasm of TNBC cells and promotes the proliferation and invasion of TNBC cells. This study aimed to explore the molecular ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(10):e0060920]

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Distinct Regulations of HO-1 Gene Expression for Stress Response and Substrate Induction.

Anqi Zhang, Takafumi Suzuki, Saki Adachi, Eriko Naganuma, Norio Suzuki, Tomonori Hosoya, Ken Itoh, Michael B Sporn, Masayuki Yamamoto,

Heme oxygenase-1 (HO-1) is the key enzyme for heme catabolism and cytoprotection. Whereas <i>HO-1</i> gene expression in response to various stresses has been investigated extensively, the precise mechanisms by which <i>HO-1</i> gene expression is regulated by the HO-1 substrate heme remain elusive. To systematically examine whether stress-mediated induction and substrate-mediated ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, :MCB0023621]

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Impaired Skin Barrier Function Due to Reduced ω-O-Acylceramide Levels in a Mouse Model of Sjögren-Larsson Syndrome.

Koki Nojiri, Shuhei Fudetani, Ayami Arai, Takuya Kitamura, Takayuki Sassa, Akio Kihara,

Sjögren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder whose causative gene encodes the fatty aldehyde dehydrogenase ALDH3A2. To date, the detailed molecular mechanism of the skin pathology of SLS has remained largely unclear. We generated double-knockout (DKO) mice for <i>Aldh3a2</i> and its homolog <i>Aldh3b2</i> (a pseudogene in humans). These mice ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(10):e0035221]

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HNRNPU-AS1 Regulates Cell Proliferation and Apoptosis via the MicroRNA 205-5p/AXIN2 Axis and Wnt/β-Catenin Signaling Pathway in Cervical Cancer.

Zhaoyuan Niu, Fengling Wang, Shihui Lv, Yingpin Lv, Ming Liu, Lei Fu, Yushuang Yao, Lingzhi Wang, Wei Lin, Fang Yuan,

Long noncoding RNAs (lncRNAs) have key functions in modulating cervical cancer (CC) genesis and progression. This work focused on exploring lncRNA HNRNPU-AS1's function in CC and the underlying mechanism. HNRNPU-AS1, AXIN2, and microRNA 205-5p (miR-205-5p) levels in CC cases were measured through reverse transcription-quantitative PCR. The relationship between miR-205-5p and ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(10):e0011521]

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A Novel cis Regulatory Element Regulates Human XIST in a CTCF-Dependent Manner.

Rini Shah, Ankita Sharma, Ashwin Kelkar, Kundan Sengupta, Sanjeev Galande,

The long noncoding RNA XIST is the master regulator for the process of X chromosome inactivation (XCI) in mammalian females. Here, we report the existence of a hitherto-uncharacterized <i>cis</i> regulatory element (cRE) within the first exon of human <i>XIST</i>, which determines the transcriptional status of <i>XIST</i> during the initiation and ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(8):e0038220]

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LINC00997/MicroRNA 574-3p/CUL2 Promotes Cervical Cancer Development via Mitogen-Activated Protein Kinase Signaling.

Daming Chu, Tengteng Liu, Yuan Yao, Nannan Luan,

Cervical cancer (CC) is a common gynecological malignancy with high morbidity and mortality. Mounting evidence has highlighted that long noncoding RNAs are essential regulators in cancer development. Long intergenic non-protein-coding RNA 997 (LINC00997) was identified for study due to its high expression in CC tissues. The aim of the study ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(8):e0005921]

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Erf Affects Commitment and Differentiation of Osteoprogenitor Cells in Cranial Sutures via the Retinoic Acid Pathway.

Angeliki Vogiatzi, Ismini Baltsavia, Emmanuel Dialynas, Vasiliki Theodorou, Yan Zhou, Elena Deligianni, Ioannis Iliopoulos, Andrew O M Wilkie, Stephen R F Twigg, George Mavrothalassitis,

ETS2 repressor factor (ERF) haploinsufficiency causes late-onset craniosynostosis (CRS) (OMIM entry 600775; CRS4) in humans, while in mice Erf insufficiency also leads to a similar multisuture synostosis phenotype preceded by mildly reduced calvarium ossification. However, neither the cell types affected nor the effects <i>per se</i> have been identified so far. ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(8):e0014921]

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Saikosaponin-d Alleviates Renal Inflammation and Cell Apoptosis in a Mouse Model of Sepsis via TCF7/FOSL1/Matrix Metalloproteinase 9 Inhibition.

Tao Yao, Lei Zhang, Ye Fu, Lina Yao, Chengjie Zhou, Guozhong Chen,

Evidence exists reporting that saikosaponin-d (Sa) can prevent experimental sepsis, and this study aims to illustrate the molecular events underlying its renoprotective effects on lipopolysaccharide (LPS)-induced renal inflammation simulating sepsis. Through network pharmacology analysis and bioinformatics analysis, we identified that Sa may influence sepsis development by mediating TCF7. Dual luciferase ... Read more >>

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(10):e0033221]

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Correction for St-Denis et al., "Evidence for Regulation of Mitotic Progression through Temporal Phosphorylation and Dephosphorylation of CK2α".

Nicole A St-Denis, D Richard Derksen, David W Litchfield,

Mol Cell Biol (Molecular and cellular biology)
[2021, 41(8):e0027421]

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