Gadd45-alpha and Gadd45-gamma utilize p38 and JNK signaling pathways to induce cell cycle G2/M arrest in Hep-G2 hepatoma cells.
The Gadd45 family of proteins, which includes alpha, beta, and gamma isoforms, has recently been shown to play a role in the G2/M cell cycle checkpoint in response to DNA damage; however, the mechanisms by which Gadd45 proteins inhibit cell cycle control are not fully understood. Using immunohistochemical analysis, we found that protein expression of Gadd45gamma, but not Gadd45alpha, was down-regulated in hepatocellular carcinoma. We thus investigated possible mechanisms by which Gadd45alpha and Gadd45gamma might differentially induce G2/M arrest in the human hepatoma Hep-G2 cell line. Flow cytometric analysis revealed significant G2/M arrest in cells transfected with either Gadd45alpha or Gadd45gamma. Importantly, we found that expression of either Gadd45alpha or Gadd45gamma activated the P38 and JNK kinase pathways to induce G2/M arrest. Taken together, these findings suggest that the induction of G2/M arrest by Gadd45alpha or Gadd45gamma involves activation of two distinct signaling pathways in Hep-G2 hepatoma cell lines.
Zhu
Na
N
Department of Microbiology, Nanjing Medical University, 210029 Nanjing, People's Republic of China.
Shao
Yan
Y
Xu
Lin
L
Yu
Long
L
Sun
Luhong
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D016195:G2 Phase / Q000502:physiology; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D009687:Nuclear Proteins; D048051:p38 Mitogen-Activated Protein Kinases; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C485654:GADD45G protein, human