[BNIP3 as an atypical representative of the Bcl-2 protein family. Part 2: Regulation of the expression and activity of BNIP3 protein and its role in tumorigenesis].
BNIP3 belongs to the Bcl-2 protein family that regulates programmed cell death. It is the only known pro-apoptotic protein expressed during hypoxia and this effect is determined by the HIF-1 responsive element in the bnip3 promoter. However, there is evidence that hypoxia is not a sufficient factor to activate BNIP3; possible cell death dependent on this protein occurs as a result of secondary effects of oxygen deprivation, such as acidosis. BNIP3 expression is also regulated by other factors, such as E2F-1, NF-kappaB, and Rb during hypoxia and nitrogen oxide during normoxia. Posttranslational modifications also seem to be essential for BNIP3 activity, but their actual significance is still unclear. Phosphorylation of BNIP3 by PKC promotes its accumulation under hypoxic conditions, but phosphorylation by CK2 can accelerate its degradation. In turn, glycosylation and interactions with anti-apoptotic Bcl-2 proteins suppress BNIP3 activity. Our knowledge about the role of BNIP3 protein in tumor progression is incomplete. It seems to be dependent on the stage of tumor progression. Tumor cells evolved multiple mechanisms of silencing BNIP3 expression or activity and promoter methylation is one of the most frequently observed among them
Swoboda
Ewelina
E
Laboratorium Immunobiologii Molekularnej Nowotworów. Instytut Immunologii i Terapii Doświadczalnej PAN im. Ludwika Hirszfelda we Wrocławiu. swoboda@iitd.pan.wroc.pl
Strzadała
Leon
L
D050687:E2F1 Transcription Factor / Q000378:metabolism; D015870:Gene Expression; D019254:Genes, bcl-2 / Q000235:genetics*; D006801:Humans; D000860:Hypoxia / Q000235:genetics*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000097782:NF-kappaB-Inducing Kinase
D050687:E2F1 Transcription Factor; D051793:Hypoxia-Inducible Factor 1; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097782:NF-kappaB-Inducing Kinase; C090121:BNIP3 protein, human