In silico modulation of apoptotic Bcl-2 proteins by mistletoe lectin-1: functional consequences of protein modifications.
The mistletoe lectin-1 (ML-1) modulates tumor cell apoptosis by triggering signaling cascades through the complex interplay of phosphorylation and O-linked N-acetylglucosamine (O-GlcNAc) modification in pro- and anti-apoptotic proteins. In particular, ML-1 is predicted to induce dephosphorylation of Bcl-2-family proteins and their alternative O-GlcNAc modification at specific, conserved Ser/Thr residues. The sites for phosphorylation and glycosylation were predicted and analyzed using Netphos 2.0 and YinOYang 1.2. The involvement of modified Ser/Thr, and among them the potential Yin Yang sites that may undergo both types of posttranslational modification, is proposed to mediate apoptosis modulation by ML-1.
Khwaja
Tasneem A
TA
Institute of Molecular Sciences and Bioinformatics, Lahore, Pakistan.
Wajahat
Tayyaba
T
Ahmad
Ishtiaq
I
Hoessli
Daniel C
DC
Walker-Nasir
Evelyne
E
Kaleem
Afshan
A
Qazi
Wajahat M
WM
Shakoori
Abdul R
AR
Din
Nasir-Ud
NU
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002415:Cats; D002417:Cattle; D017124:Conserved Sequence; D006224:Cricetinae; D003412:Cricetulus; D003670:Deer; D004285:Dogs; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D028321:Plant Preparations / Q000494:pharmacology*; D010940:Plant Proteins / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D054790:Ribosome Inactivating Proteins, Type 2 / Q000494:pharmacology*; D016415:Sequence Alignment; D012756:Sheep; D013045:Species Specificity; D014118:Toxins, Biological / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D051025:bcl-Associated Death Protein / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology
D028321:Plant Preparations; D010940:Plant Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C488862:mistletoe lectin I