LIM domain protein FHL1B interacts with PP2A catalytic β subunit--a novel cell cycle regulatory pathway

Four-and-a-half LIM domain protein 1B (FHL1B) is an alternatively-spliced isoform of FHL1. In this study, FHL1B was demonstrated to interact with the β catalytic subunit (Cβ) of a type 2A protein phosphatase (PP2A) by yeast two-hybrid screening. Domain studies using a small-scale yeast two-hybrid interaction assay revealed the mediation of protein-protein interaction by FHL1B’s C-terminus. Interaction between FHL1B and PP2A was further verified by co-immunoprecipitation. FHL1B was also shown to shuttle between nucleus and cytoplasm at different phases of the cell cycle. These data suggest that the FHL1B/PP2A_Cβ interaction may illustrate a novel cell-cycle regulatory pathway.

Structured summary

MINT-8044739: FHL1B (uniprotkb:Q13642-2) physically interacts (MI:0915) with PP2Acbeta (uniprotkb:P62714) by two hybrid (MI:0018)MINT-8044769, MINT-8044778: FHL1B (uniprotkb:Q13642-2) physically interacts (MI:0915) with PP2Acbeta (uniprotkb:P62714) by anti bait coimmunoprecipitation (MI:0006)     

Cell cycle regulation of the mammalian CDK activator RINGO/Speedy A

Cell cycle progression is regulated by cyclin-dependent kinases (CDKs), whose activation requires the binding of regulatory subunits named cyclins. RINGO/Speedy A is a mammalian protein that has no amino acid sequence homology with cyclins but can activate CDKs. Here we show that RINGO/Speedy A is a highly unstable protein whose expression and phosphorylation are periodically regulated during the cell cycle. RINGO/Speedy A is degraded by the proteasome and the process involves the ubiquitin ligase SCF^Skp2. Overexpression of a stabilized RINGO/Speedy A form results in the accumulation of high levels of RINGO/Speedy A at late stages of mitosis, which interfere with cytokinesis and chromosome decondensation. Our data show that tight regulation of RINGO/Speedy A is important for the somatic cell cycle.

Structured summary

MINT-7226413:RINGO A (uniprotkb:Q5MJ70) physically interacts (MI:0914) with Ubiquitin (uniprotkb:P62988) by anti bait coimmunoprecipitation (MI:0006)MINT-7226431, MINT-7226448:RINGO A (uniprotkb:Q5MJ70) physically interacts (MI:0914) with Skp2 (uniprotkb:Q13309) by anti tag coimmunoprecipitation (MI:0007)     

CSN5/Jab1 controls multiple events in the mammalian cell cycle

The COP9 signalosome (CSN) complex is critical for mammalian cell proliferation and survival, but it is not known how the CSN affects the cell cycle. In this study, MEFs lacking CSN5/Jab1 were generated using a CRE-flox system. MEFs ceased to proliferate upon elimination of CSN5/Jab1. Rescue experiments indicated that the JAMM domain of CSN5/Jab1 was essential. CSN5/Jab1-elimination enhanced the neddylation of cullins 1 and 4 and altered the expression of many factors including cyclin E and p53. CSN5/Jab1-elimination inhibited progression of the cell cycle at multiple points, seemed to initiate p53-independent senescence and increased the ploidy of cells. Thus, CSN5/Jab1 controls different events of the cell cycle, preventing senescence and endocycle as well as the proper progression of the somatic cell cycle.

Structured summary

MINT-8046253: Csn1 (uniprotkb:Q99LD4) physically interacts (MI:0914) with Csn5 (uniprotkb:O35864), Csn8 (uniprotkb:Q8VBV7), Csn3 (uniprotkb:O88543), Csn7b (uniprotkb:Q8BV13) and Csn6 (uniprotkb:O88545) by anti bait coimmunoprecipitation (MI:0006)     

MCC, a new interacting protein for Scrib, is required for cell migration in epithelial cells

To further characterize the molecular events supporting the tumor suppressor activity of Scrib in mammals, we aim to identify new binding partners. We isolated MCC, a recently identified binding partner for β-catenin, as a new interacting protein for Scrib. MCC interacts with both Scrib and the NHERF1/NHERF2/Ezrin complex in a PDZ-dependent manner. In T47D cells, MCC and Scrib proteins colocalize at the cell membrane and reduced expression of MCC results in impaired cell migration. By contrast to Scrib, MCC inhibits cell directed migration independently of Rac1, Cdc42 and PAK activation. Altogether, these results identify MCC as a potential scaffold protein regulating cell movement and able to bind Scrib, β-catenin and NHERF1/2.

Structured summary

MINT-7211022: SCRIB (uniprotkb:Q14160) and MCC (uniprotkb:P23508) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7210609: SCRIB (uniprotkb:Q14160) physically interacts (MI:0915) with MCC (uniprotkb:P23508) by two hybrid (MI:0018)MINT-7210759, MINT-7210792: SCRIB (uniprotkb:Q14160) physically interacts (MI:0914) with PIX beta (uniprotkb:Q14155) by pull down (MI:0096)MINT-7210883, MINT-7210820: SCRIB (uniprotkb:Q14160) physically interacts (MI:0914) with MCC (uniprotkb:P23508) by anti bait coimmunoprecipitation (MI:0006)MINT-7210634, MINT-7210690, MINT-7210731: SCRIB (uniprotkb:Q14160) physically interacts (MI:0914) with MCC (uniprotkb:P23508) by pull down (MI:0096)MINT-7211267: E6 (uniprotkb:P06463) physically interacts (MI:0915) with SCRIB (uniprotkb:Q14160), SNX27 (uniprotkb:Q96L92), UTRN (uniprotkb:P46939), CASK (uniprotkb:O14936), DMD (uniprotkb:P11532) and Dlg (uniprotkb:Q12959) by pull down (MI:0096)MINT-7211237: MCC (uniprotkb:P23508) physically interacts (MI:0915) with SCRIB (uniprotkb:Q14160), EZR (uniprotkb:P15311), SNX27 (uniprotkb:Q96L92), NHERF1 (uniprotkb:O14745) and NHERF2 (uniprotkb:Q15599) by pull down (MI:0096)     

Per3, a circadian gene, is required for Chk2 activation in human cells

PER3 is a member of the PERIOD genes, but does not play essential roles in the circadian clock. Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells. In addition, Per3 physically interacted with ATM and Chk2. Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage, and this activation depended on ATM. Per3 overexpression also led to the inhibition of cell proliferation and apoptotic cell death. These combined results suggest that Per3 is a checkpoint protein that plays important roles in checkpoint activation, cell proliferation and apoptosis.

Structured summary

MINT-8052850: Chk2 (uniprotkb:O96017) physically interacts (MI:0915) with Per3 (uniprotkb:P56645) by anti bait coimmunoprecipitation (MI:0006)MINT-8052875: Per3 (uniprotkb:P56645) physically interacts (MI:0914) with Chk2 (uniprotkb:O96017) and ATM (uniprotkb:Q13315) by anti tag coimmunoprecipitation (MI:0007)     

Role of p53/FAK association and p53 phosphorylation in staurosporine-mediated apoptosis: Wild type versus mutant p53-R175H

A novel survival role of focal adhesion kinase (FAK) that involves its nuclear translocation and direct association with p53 has been demonstrated. Here we examined the relationship between the p53/FAK interaction and Ser46 phosphorylation of p53 (p-p53^Ser46) in the apoptotic regulation of human esophageal squamous cell carcinoma (HOSCC) cell lines, expressing either wild type (wt) p53 or mutant (mt) p53-R175H. In contrast to the wt p53 cell lines, the mt p53-R175H cell line was resistant to staurosporine (STS)-mediated detachment and caspase-3 activation. Furthermore, despite the resistance of mt p53-R175H to Ser46 phosphorylation, both wt and mt HOSCC cells translocate FAK into the nucleus and maintain the p53/FAK interaction post STS treatment. These findings provide unique insight into how tumor cells harboring the R175H mutant may resist chemotherapeutic intervention.

Structured summary

MINT-7294020: FAK (uniprotkb:Q05397) physically interacts (MI:0915) with p53 (uniprotkb:P04637) by anti-bait coimmunoprecipitation (MI:0006)     

UV-induced interaction between p38 MAPK and p53 serves as a molecular switch in determining cell fate

p53 plays a fundamental role in the maintenance of genome integrity after DNA damage, deciding whether cells repair and live, or die. However, the rules that govern its choice are largely undiscovered. Here we show that the functional relationship between p38 and p53 is crucial in defining the cell fate after DNA damage. Upon low dose ultraviolet (UV) radiation, p38 and p53 protect the cells from apoptosis separately. Conversely, they function together to favor apoptosis upon high dose UV exposure. Taken together, a UV-induced, dose-dependent interaction between p38 and p53 acts as a switch to determine cell fate.

Structured summary

MINT-8050838: p53 (uniprotkb:P02340) physically interacts (MI:0915) with p38 (uniprotkb:P47811) by anti bait coimmunoprecipitation (MI:0006)MINT-8050948: p53 (uniprotkb:P04637) physically interacts (MI:0915) with p38 (uniprotkb:P47811) by anti tag coimmunoprecipitation (MI:0007)     

Myosin 1G (Myo1G) is a haematopoietic specific myosin that localises to the plasma membrane and regulates cell elasticity

Immune cells navigate through different environments where they experience different mechanical forces. Responses to external forces are determined by the mechanical properties of a cell and they depend to a large extent on the actin-rich cell cortex. We report here that Myo1G, a previously uncharacterised member of class I myosins, is expressed specifically in haematopoietic tissues and cells. It is associated with the plasma membrane. This association is dependent on a conserved PH-domain-like myosin I tail homology motif and the head domain. However, the head domain does not need to be a functional motor. Knockdown of Myo1G in Jurkat cells decreased cell elasticity significantly. We propose that Myo1G regulates cell elasticity by deformations of the actin network at the cell cortex.

Structured summary

MINT-7307273: MYO1G (uniprotkb:B0I1T2) and Actin (uniprotkb:P60709) colocalize (MI:0403) by fluorescence microscopy (MI:0416) MINT-7307283: TfR (uniprotkb:P02786) and MYO1G (uniprotkb:B0I1T2) colocalize (MI:0403) by cosedimentation through density gradients (MI:0029)     

CAP (Cbl associated protein) regulates receptor-mediated endocytosis

CAP (c-Cbl associated protein)/ponsin belongs to a family of adaptor proteins implicated in cell adhesion and signaling. Here we show that CAP binds to and co-localizes with the essential endocytic factor dynamin. We demonstrate that CAP promotes the formation of dynamin-decorated tubule like structures, which are also coated with actin filaments. Accordingly, we found that the expression of CAP leads to the inhibition of dynamin-mediated endocytosis and increases EGFR stability. Thus, we suggest that CAP may coordinate the function of dynamin with the regulation of the actin cytoskeleton during endocytosis.

Structured summary:

MINT-6804322: CAP (uniprotkb:Q9BX66) physically interacts (MI:0218) with Cbl (uniprotkb:Q8K4S7) and dynamin 2 (uniprotkb:P39052) by pull down (MI:0096)MINT-6804285: CAP (uniprotkb:Q9BX66) physically interacts (MI:0218) with FAK (uniprotkb:O35346), vinculin (uniprotkb:P85972) and dynamin 2 (uniprotkb:P39052) by pull down (MI:0096)MINT-6804245, MINT-6804259, MINT-6804272: CAP (uniprotkb:Q9BX66) physically interacts (MI:0218) with dynamin 2 (uniprotkb:P39052) by pull down (MI:0096)MINT-6804344: CAP (uniprotkb:Q9BX66) physically interacts (MI:0218) with dynamin 2 (uniprotkb:P50570) by anti tag coimmunoprecipitation (MI:0007)MINT-6804371: dynamin 1 (uniprotkb:P21575) physically interacts (MI:0218) with CAP (uniprotkb:O35413) by anti bait coimmunoprecipitation (MI:0006)MINT-6804446, MINT-6804464: F-actin (uniprotkb:P60709), CAP (uniprotkb:Q9BX66) and dynamin 2 (uniprotkb:P50570) colocalize (MI:0403) by fluorescence microscopy (MI:0416)     

The β1 subunit of Na/K-ATPase interacts with BKCa channels and affects their steady-state expression on the cell surface

Large conductance Ca²⁺-activated K⁺ channels (BK_Ca) encoded by the Slo1 gene play a role in the physiological regulation of many cell types. Here, we show that the β1 subunit of Na⁺/K⁺-ATPase (NKβ1) interacts with the cytoplasmic COOH-terminal region of Slo1 proteins. Reduced expression of endogenous NKβ1 markedly inhibits evoked BK_Ca currents with no apparent effect on their gating. In addition, NKβ1 down-regulated cells show decreased density of Slo1 subunits on the cell surface.

Structured summary

MINT-7260438, MINT-7260555: Slo1 (uniprotkb:Q8AYS8) physically interacts (MI:0915) with NKbeta1 (uniprotkb:P08251) by anti bait coimmunoprecipitation (MI:0006)MINT-7260587, MINT-7260606, MINT-7260619, MINT-7260632: Slo1 (uniprotkb:Q08460) physically interacts (MI:0915) with NKbeta 1 (uniprotkb:P08251) by pull down (MI:0416)MINT-7260570: NKbeta1 (uniprotkb:P08251) and Slo1 (uniprotkb:Q8AYS8) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7260414: Slo1 (uniprotkb:Q08460) physically interacts (MI:0915) with NKbeta1 (uniprotkb:P08251) by two hybrid (MI:0018)     

Interaction of testisin with maspin and its impact on invasion and cell death resistance of cervical cancer cells

Previous studies have shown that testisin promotes malignant transformation in cancer cells. To define the mechanism of testisin-induced carcinogenesis, we performed yeast two-hybrid analysis and identified maspin, a tumor suppressor protein, as a testisin-interacting molecule. The direct interaction and cytoplasmic co-localization of testisin with maspin was confirmed by immunoprecipitation and confocal analysis, respectively. In cervical cancer cells, maspin modulated cell death and invasion; however, these effects were inhibited by testisin in parallel experiments. Of interest, the doxorubicin resistance was dramatically reduced by testisin knockdown (P = 0.016). Moreover, testisin was found to be over-expressed in cervical cancer samples as compared to matched normal cervical tissues. Thus, we postulate that testisin may promote carcinogenesis by inhibiting tumor suppressor activity of maspin.

Structured summary

MINT-7712215, MINT-7712176: Testisin (uniprotkb:Q9Y6M0) binds (MI:0407) to Maspin (uniprotkb:P36952) by pull down (MI:0096)MINT-7712188: Testisin (uniprotkb:Q9Y6M0) and Maspin (uniprotkb:P36952) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7712115: Testisin (uniprotkb:Q9Y6M0) physically interacts (MI:0915) with Maspin (uniprotkb:P36952) by two-hybrid (MI:0018)MINT-7712162, MINT-7712128: Maspin (uniprotkb:P36952) physically interacts (MI:0915) with Testisin (uniprotkb:Q9Y6M0) by anti bait co-immunoprecipitation (MI:0006)MINT-7712147: Testisin (uniprotkb:Q9Y6M0) physically interacts (MI:0915) with Maspin (uniprotkb:P36952) by anti tag co-immunoprecipitation (MI:0007)     

Rab35 regulates neurite outgrowth and cell shape

Recent studies have identified Rab35 in the endocytic pathway and as a regulator of cytokinesis; however its molecular mechanisms are currently unknown. Here, we find that Rab35 colocalizes with actin filaments and with Cdc42, Rac1 and RhoA, and that Rab35 can activate Cdc42 both in vivo and in vitro. We find activated Rab35 stimulates neurite outgrowth in PC12 and N1E-115 cells via a Cdc42-dependent pathway and that siRNA knockdown of Rab35 activity abolishes neurite outgrowth in these cell lines. We conclude that one function of Rab35 is to regulate Rho-family GTPases and that this role has consequences for neurite outgrowth.

Structured summary

MINT-7012081: Rac1(uniprotkb:P63000) and Rab 35 (uniprotkb:Q15286) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7012070: actin (uniprotkb:P60709) and Rab 35 (uniprotkb:Q15286) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7012095: cdc42 (uniprotkb:P60953) and Rab 35 (uniprotkb:Q15286) colocalize (MI:0403) by fluorescence microscopy (MI:0416)     

Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regulatory subunit of PI-3 kinase in regulation of macropinocytosis in LNCaP cells

Macropinocytosis is regulated by Abl kinase via an unknown mechanism. We previously demonstrated that Abl kinase activity is, itself, regulated by Abi1 subsequent to Abl kinase phosphorylation of Abi1 tyrosine 213 (pY213) [1]. Here we show that blocking phosphorylation of Y213 abrogated the ability of Abl to regulate macropinocytosis, implicating Abi1 pY213 as a key regulator of macropinocytosis. Results from screening the human SH2 domain library and mapping the interaction site between Abi1 and the p85 regulatory domain of PI-3 kinase, coupled with data from cells transfected with loss-of-function p85 mutants, support the hypothesis that macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85—thereby linking Abl kinase signaling to p85-dependent regulation of macropinocytosis.

Structured summary

MINT-7908602: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to SHIP2 (uniprotkb:O15357) by array technology (MI:0008)MINT-7908362: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Emt (uniprotkb:Q08881) by array technology (MI:0008)MINT-7908235: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Lyn (uniprotkb:P07948) by array technology (MI:0008)MINT-7908075: Abi1 (uniprotkb:Q8IZP0)binds (MI:0407) to Fgr (uniprotkb:P09769) by array technology (MI:0008)MINT-7908330, MINT-7908522: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Vav1 (uniprotkb:P15498) by array technology (MI:0008)MINT-7907962: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Fyn (uniprotkb:P06241) by array technology (MI:0008)MINT-7908203: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Src (uniprotkb:P12931) by array technology (MI:0008)MINT-7908570: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to SHP-2 (uniprotkb:P35235) by array technology (MI:0008)MINT-7908187, MINT-7908586: Abi1(uniprotkb:Q8IZP0) binds (MI:0407) to Gap (uniprotkb:P20936) by array technology (MI:0008)MINT-7907981, MINT-7907995: Abi1 (uniprotkb:Q8IZP0) physically interacts (MI:0915) with p85a (uniprotkb:P26450) by anti tag coimmunoprecipitation (MI:0007)MINT-7908251: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to PLCG1 (uniprotkb:P19174) by array technology (MI:0008)MINT-7908346: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Grb2 (uniprotkb:P62993) by array technology (MI:0008)MINT-7907945: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Abl (uniprotkb:P00519) by array technology (MI:0008)MINT-7908474: Abi1 (uniprotkb:Q8IZP0)binds (MI:0407) to p85b (uniprotkb:O00459) by array technology (MI:0008)MINT-7908107: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Hck (uniprotkb:P08631) by array technology (MI:0008)MINT-7908011: p85a (uniprotkb:P26450) physically interacts (MI:0915) with Abi1 (uniprotkb:Q8IZP0) by pull down (MI:0096)MINT-7908155: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to FynT (uniprotkb:P06241-2) by array technology (MI:0008)MINT-7908283, MINT-7908490: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to p55g (uniprotkb:Q92569) by array technology (MI:0008)MINT-7907929, MINT-7907815, MINT-7907832, MINT-7907865, MINT-7907897, MINT-7907913, MINT-7907881, MINT-7907848: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to p85a (uniprotkb:P27986) by array technology (MI:0008)MINT-7908059: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Frk (uniprotkb:P42685) by array technology (MI:0008)MINT-7908378: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to CblC (uniprotkb:Q9ULV8) by array technology (MI:0008)MINT-7908618: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to CblA (uniprotkb:B5MC15) by array technology (MI:0008)MINT-7908139, MINT-7908538: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Nap4 (uniprotkb:O14512) by array technology (MI:0008)MINT-7908426: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to CblB (uniprotkb:Q13191) by array technology (MI:0008)MINT-7908506: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Crk (uniprotkb:P46108) by array technology (MI:0008)MINT-7908554: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to mAbl (uniprotkb:P00520) by array technology (MI:0008)MINT-7908043, MINT-7908394: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Vav2 (uniprotkb:P52735) by array technology (MI:0008)MINT-7908458: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to mSck/ShcB (uniprotkb:Q8BMC3) by array technology (MI:0008)MINT-7908091: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Yes (uniprotkb:P07947) by array technology (MI:0008)MINT-7908219: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Src (uniprotkb:P00523) by array technology (MI:0008)MINT-7908123: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Fer (uniprotkb:P16591) by array technology (MI:0008)MINT-7908410: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to CrkL (uniprotkb:P46109) by array technology (MI:0008)MINT-7908314, MINT-7908442: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Arg (uniprotkb:P42684) by array technology (MI:0008)MINT-7908299: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to PLCG1 (uniprotkb:P10686) by array technology (MI:0008)MINT-7908171: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Fes (uniprotkb:P07332) by array technology (MI:0008)MINT-7908027: Abi1 (uniprotkb:Q8IZP0) binds (MI:0407) to Lck (uniprotkb:P06239) by array technology (MI:0008)     

HO1 and PcyA proteins involved in phycobilin biosynthesis form a 1:2 complex with ferredoxin-1 required for photosynthesis

The HO1 and PcyA genes, encoding heme oxygenase-1 (HO1) and phycocyanobilin (PCB):ferredoxin (Fd) oxidoreductase (PcyA), respectively, are required for chromophore synthesis in photosynthetic light-harvesting complexes, photoreceptors, and circadian clocks. In the PCB biosynthetic pathway, heme first undergoes cleavage to form biliverdin. I confirmed that Fd1 induced the formation of a stable and functional HO1 complex by the gel mobility shift assay. Furthermore, analysis by a chemical cross-linking technique designed to detect protein-protein interactions revealed that HO1 and PcyA directly interact with Fd in a 1:2 ratio. Thus, Fd1, a one-electron carrier protein in photosynthesis, drives the phycobilin biosynthetic pathway.

Structured summary

MINT-7014657: Fd1 (uniprotkb:P0A3C9) and HO1 (uniprotkb:Q8DLW1) bind (MI:0407) by comigration in non-denaturing gel electrophoresis (MI:0404)MINT-7014666: HO1 (uniprotkb:Q8DLW1 and Fd1 (uniprotkb:P0A3C9) bind (MI:0407) by cross-linking studies (MI:0030)MINT-7014675: PcyA (uniprotkb:P59288) and Fd1 (uniprotkb:P0A3C9) bind (MI:0407) by cross-linking studies (MI:0030)     

p53 inhibits tumor cell invasion via the degradation of snail protein in hepatocellular carcinoma

The tumor suppressor protein p53 is a key regulator of cell cycle arrest and apoptosis. Snail protein regulates cancer-associated malignancies. However, the relationship between p53 and Snail proteins in hepatocellular carcinoma (HCC) has not been completely understood. To determine whether Snail and p53 contribute to hepatocarcinogenesis, we analyzed the expression of Snail proteins in p53-overexpressing HCC cells. We found that p53 wild-type (WT) induced the degradation of Snail protein via murine double minute 2-mediated ubiquitination, whereas p53 mutant did not induce Snail degradation. As we expected, only p53WT induced endogenous Snail protein degradation and inhibited tumor cell invasion. These findings contribute to a better understanding of the role of p53 mutation and Snail overexpression as a late event in hepatocarcinogenesis.

Structured summary

MINT-7718917: p53 (uniprotkb:P04637) physically interacts (MI:0915) with Snai1 (uniprotkb:O95863) by anti bait coimmunoprecipitation (MI:0006)MINT-7719877: Snai1 (uniprotkb:O95863) physically interacts (MI:0915) with ubiquitin (uniprotkb:P62988) by anti tag coimmunoprecipitation (MI:0007)MINT-7718928: Snai1 (uniprotkb:O95863) physically interacts (MI:0915) with p53 (uniprotkb:P04637) by anti tag coimmunoprecipitation (MI:0007)MINT-7718939: Snai1 (uniprotkb:O95863) physically interacts (MI:0915) with MDM2 (uniprotkb:Q00987) by anti tag coimmunoprecipitation (MI:0007)