Molecule Information

General Information of the Molecule (ID: Mol04411)

• Name: Bcl-2 homologous antagonist/killer (BAK1) ,Homo sapiens
• Synonyms: Apoptosis regulator BAK; Bcl-2-like protein 7
• Molecule Type: Protein
• Gene Name: BAK1
• Gene ID: 578
• Sequence:
  MASGQGPGPPRQECGEPALPSASEEQVAQDTEEVFRSYVFYRHQQEQEAEGVAAPADPEM
  VTLPLQPSSTMGQVGRQLAIIGDDINRRYDSEFQTMLQHLQPTAENAYEYFTKIATSLF
  E SGINWGRVVALLGFGYRLALHVYQHGLTGFLGQVTRFVVDFMLHHCIARWIAQRGGWV
  AA LNLGNGPILNVLVVLGVVLLGQFVVRRFFKS
• Function: Plays a role in the mitochondrial apoptotic process. Uponarrival of cell death signals, promotes mitochondrial outer membrane permeabilization by oligomerizing to form pores within the MOM.This releases apoptogenic factors into the cytosol, includingcytochrome c, promoting the activation of caspase 9 which in turnprocesses and activates the effector caspases.{ECO:0000269|PubMed:17157251, ECO:0000269|PubMed:8521816}.
• Uniprot ID: BAK_HUMAN
• Ensembl ID: ENSG0000003011014
• HGNC ID: HGNC:949

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Venetoclax

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Diffuse large B-cell lymphoma [ICD-11: 2A81.0] [1]

• Resistant Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Resistant Drug: Venetoclax
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Apoptosis signaling pathway; Inhibition; hsa04210
• In Vitro Model: SU-DHL-2 cells; N.A.; Homo sapiens (Human); CVCL_9950
• In Vitro Model: SUDHL4 cells; Blood; Homo sapiens (Human); CVCL_0539
• In Vitro Model: SUDHL5 cells; Blood; Homo sapiens (Human); CVCL_1735
• In Vitro Model: SUDHL6 cells; Blood; Homo sapiens (Human); CVCL_2206
• In Vitro Model: SUDHL8 cells; Blood; Homo sapiens (Human); CVCL_2207
• In Vitro Model: SUDHL10 cells; Blood; Homo sapiens (Human); CVCL_1889
• In Vitro Model: SUDHL16 cells; Blood; Homo sapiens (Human); CVCL_1890
• In Vitro Model: Toledo cells; Peripheral blood; Homo sapiens (Human); CVCL_3611
• Experiment for Molecule Alteration: Western blot assay; RNA Sequencing assay; Flow cytometry
• Experiment for Drug Resistance: Cell survival and synergy assay; Caspase-3/7 apoptosis assay; Live/Dead assay
• Mechanism Description: Our findings demonstrate that multiple, complex mechanisms of venetoclax resistance can emerge in DLBCL. However, our elucidation of the increased vulnerability of venetoclax-resistant DLBCL to ETC complex I and IDH2 inhibition revealed potential new treatment approaches to overcome venetoclax resistance. Although there is still interest in adding venetoclax to decrease the threshold of apoptosis in the therapeutic armamentarium for DLBCL as a combination therapy, targeting other BCL2 family members, such as BCLW and BFL1, for which there are currently no specific targeted agents, could also be an option.

References

• Ref 1: Identifying Targetable Vulnerabilities to Circumvent or Overcome Venetoclax Resistance in Diffuse Large B-Cell Lymphoma. Cancers (Basel). 2024 Jun 3;16(11):2130.